The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index; 46 of the 84 sources its claims cite were checked for support.
Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier
Open accessAbstract
According to the neurovascular hypothesis, impairment of low-density lipoprotein receptor-related protein-1 (LRP1) in brain capillaries of the blood-brain barrier (BBB) contributes to neurotoxic amyloid-β (Aβ) brain accumulation and drives Alzheimer's disease (AD) pathology. However, due to conflicting reports on the involvement of LRP1 in Aβ transport and the expression of LRP1 in brain endothelium, the role of LRP1 at the BBB is uncertain. As global Lrp1 deletion in mice is lethal, appropriate models to study the function of LRP1 are lacking. Moreover, the relevance of systemic Aβ clearance to AD pathology remains unclear, as no BBB-specific knockout models have been available. Here, we developed transgenic mouse strains that allow for tamoxifen-inducible deletion of Lrp1 specifically within brain endothelial cells (Slco1c1-CreER(T2) Lrp1(fl/fl) mice) and used these mice to accurately evaluate LRP1-mediated Aβ BBB clearance in vivo. Selective deletion of Lrp1 in the brain endothelium of C57BL/6 mice strongly reduced brain efflux of injected [125I] Aβ(1-42). Additionally, in the 5xFAD mouse model of AD, brain endothelial-specific Lrp1 deletion reduced plasma Aβ levels and elevated soluble brain Aβ, leading to aggravated spatial learning and memory deficits, thus emphasizing the importance of systemic Aβ elimination via the BBB. Together, our results suggest that receptor-mediated Aβ BBB clearance may be a potential target for treatment and prevention of Aβ brain accumulation in AD.
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TL;DR
Using brain endothelial–specific inducible Lrp1 knockout mice, the authors show that endothelial LRP1 mediates a substantial fraction of Aβ1–42 efflux across the blood-brain barrier and regulates soluble brain Aβ. In 5xFAD mice, loss of endothelial Lrp1 reduced plasma Aβ, elevated soluble brain Aβ, and worsened spatial learning and memory.
Key findings
- In vitro, Lrp1-deficient brain endothelial cells transcytosed approximately 50% less [125I]Aβ1–42 than controls; the LRP1-mediated contribution increased from 49.2% at 0.1 nM Aβ to 65.4% at 5 nM Aβ.
- In vivo, brain endothelial Lrp1 deletion reduced rapid BBB transport of 5.14 nM [125I]Aβ1–42 by about 48%; LRP1 mediated 47.5% of Aβ1–42 BBB clearance and approximately 27% of total Aβ1–42 clearance, and knockout mice needed about 4 times longer to clear about 70% of injected Aβ (60 minutes vs. 15 minutes).
- In 7-month-old 5xFAD Lrp1 BE−/− mice, plasma Aβ1–40 and Aβ1–42 were reduced and soluble brain Aβ was elevated (immunoprecipitation: about 2.5-fold for Aβ1–42 and 3.7-fold for Aβ1–40; ELISA: about 4.8-fold for Aβx–40 and 3.1-fold for Aβx–42; insoluble Aβx–40 about 2.0-fold), with impaired spatial learning and spatial reference memory.
- LRP1 preferentially cleared Aβ1–40: in 5xFAD Lrp1 BE fl/fl mice, brain Aβ1–42/Aβ1–40 ratios were elevated and plasma ratios lowered; no significant differences in plaque load or gliosis were found.
Methods
- Generated tamoxifen-inducible brain endothelial–specific Lrp1 knockout mice (Slco1c1-CreER T2 × Lrp1 fl/fl; Lrp1 BE−/−) and crossed them with 5xFAD mice, using littermate controls.
- In vitro transcytosis assays used primary mouse brain capillary endothelial monolayers with [125I]Aβ1–42 (0.05–5 nM) and [14C]-inulin; in vivo brain efflux index used caudate putamen injection of 5.14 nM [125I]Aβ1–42 plus [14C]-inulin, with CSF and plasma sampling.
- Aβ species were measured by immunoprecipitation/Western blot and ELISA; plaque load, astrogliosis, and microgliosis by immunohistochemistry; spatial learning and memory by Morris water maze; statistics used unpaired t tests and ANOVA with Bonferroni comparisons.
Limitations
- Stated: prior conflicting LRP1 findings may arise from supraphysiological Aβ injections into different brain regions or from in vitro studies using epithelial cells such as MDCK and CHO cells; LRP1 function may depend on cell type and polarization state.
- Stated: in 7-month-old 5xFAD mice, no significant differences in plaque deposition or gliosis were detected, and the trend toward higher insoluble Aβx–42 did not reach statistical significance.
- Evident: conclusions rely on mouse models (C57BL/6 and 5xFAD), with small behavioral groups (n = 5–7 per group in the Morris water maze) and a single in vivo Aβ1–42 concentration/time course; no human validation is presented.
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Claims the paper makes
60 Own result · 19 Own interpretation · 18 Partly supported · 13 Own method · 11 No full text of the sources · 9 Supported · 6 No basis given · 4 Supported so far · 3 Not checked yet · 2 Sources not found · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Recent studies suggest that transport across the BBB is a major elimination route for brain Aβ (8,11,12,15).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
What the sources say
- Supportedcites [8] source
The Discussion (p. 7) states that transport across the BBB into the vascular system was the major component of Aβ efflux from the CNS. The paper’s conclusion (p. 10) likewise describes this transport as a potentially major physiological mechanism for preventing brain Aβ accumulation. Its experiments specifically examined Aβ1-40 clearance in mice. (LLM, conf=0.94)
- Supportedcites [11] Bell, 2007, Transport pathways for clearance of human Alzheimer’s amyloid β-peptide and apolipoproteins E and J in the mouse central nervous system, J Cereb Blood Flow Metab source
The Results state that BBB transport is a major efflux route for human Aβ40 from the mouse CNS, with an efflux rate more than six times that of transport via interstitial-fluid flow. The paper also reports BBB efflux of Aβ42, though at a slower rate. This supports the citing sentence’s hedged claim. (LLM, conf=0.94)
- Supportedcites [12] source
The Introduction describes LRP1 as a major Aβ efflux transporter at the BBB. The Results report that, in the paper’s mouse-brain experiments, more than 85% of free Aβ40 was eliminated across the BBB at 90 minutes, supporting the cited statement that BBB transport is a major elimination route. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [15] Deane, 2004, RAGE (yin) versus LRP (yang) balance regulates alzheimer amyloid beta-peptide clearance through transport across the blood-brain barrier, Stroke source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Supported
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In the paper
“LRP1 expression decreases in total brain and brain capillaries with age (8,9).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
What the sources say
- Partly supportedcites [8] sourceExperimental — accuracy not yet measured
The mouse results (p. 7; Figure 6, p. 8) show fewer LRP-1-positive brain microvessels, including capillaries, at 9 months than at 2 months. They do not establish a decrease in total-brain LRP-1 expression: staining in parenchymal cells showed only a nonsignificant downward trend. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [9] source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
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In the paper
“Recent evidence suggests that in the common sporadic or late-onset forms of AD and in some cases of familiar AD (FAD) elevated Aβ brain levels result from impaired clearance instead of overproduction (1).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
What the sources say
- Partly supportedcites [1] sourceExperimental — accuracy not yet measured
The Abstract reports impaired Aβ42 and Aβ40 clearance in late-onset AD, with no average difference in production rates. It does not establish this mechanism for any familial AD cases; the paper instead notes that genetic alterations increase Aβ production in rare cases. It also cautions that the observed association does not prove causality. (LLM, conf=0.88)
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Moreover, LRP1 is further reduced in AD (8,10).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
What the sources say
- Supportedcites [8] source
The Figure 7 caption (p. 9) reports fewer vessels staining for LRP-1 and less intense staining in frontal cortex from AD patients than from controls. The discussion (p. 10) also describes vascular LRP-1 downregulation in AD brains relative to age-matched controls. (LLM, conf=0.92)
- Supportedcites [10] source
The Discussion states that LRP levels decline with age in controls and are further reduced in AD subjects. The reported measurements also found approximately twofold lower levels in AD brains than in age-matched controls. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
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In the paper
“These mice express 5 FAD mutations under Thy-1 promotor control to increase overall Aβ 1-42 production in the brain (37).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
What the sources say
- Supportedcites [37] source
The “5XFAD mice: rapid amyloid pathology models” section states that the five FAD mutations are expressed with the neuron-specific Thy1 promoter and that 5XFAD mice produce massive cerebral Aβ42 levels. The “Transgenic strategy and generation of 5XFAD mice” section also describes the mutations and their effect on Aβ42 production. (LLM, conf=0.94)
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In the paper
“NeuNpositive neurons showed strong LRP1 expression in the soma of neurons (Figure 3A), validating high LRP1 expression in neuronal cell bodies as reported previously (28,29).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
What the sources say
- Supportedcites [28] source
Section VIII.B, “LRP1 expression in the brain,” states that LRP1 immunoreactivity is abundant on neuronal cell bodies in the adult human brain. This supports the previously reported cell-body expression for which the source is cited; the NeuN staining is the citing paper’s own observation. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [29] Wolf, 1992, Characterization and immunohistochemical localization of α2-macroglobulin receptor (low-density lipoprotein receptor-related protein) in human brain, Am J Pathol
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“We detected that rapid BBB transport was reduced by about 48% in Lrp1 BE -/-mice (Figure 6C), whereas clearance through slow ISF bulk flow, a minor component of Aβ brain efflux (8), was not altered (Figure 6B).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
What the sources say
- Supportedcites [8] source
Citation (8) supports the description of slow ISF bulk flow as a minor component of amyloid-β efflux. The Results (p. 4) report that ISF bulk flow accounted for 10.7% of efflux, versus 73.8% through BBB transport. The statement that clearance was unchanged in Lrp1 BE-/- mice is the citing authors’ own Figure 6B result, not a finding attributed to this source. (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, with an endocytosis rate up to 16 times faster than that of other Aβ receptors, such as VDLDR or LDLR (12,35), LRP1 may outperform other receptors in Aβ clearance, especially at higher concentrations.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
What the sources say
- Partly supportedcites [12] sourceExperimental — accuracy not yet measured
The Introduction describes LRP1 as a major transporter for rapid Aβ clearance at the blood–brain barrier, and the Results report faster LRP1-mediated than VLDLR-mediated internalization for the studied apoE2 and apoE3 pathways. Our copy does not establish that LRP1 outperforms other receptors specifically at higher Aβ concentrations; it also finds that Aβ–apoE4 clearance depends on VLDLR, not LRP1. No page numbers are available in the indexed passages. (LLM, conf=0.85)
- Partly supportedcites [35] sourceExperimental — accuracy not yet measured
The Results (page unavailable) show that LRP internalizes the tested ligands much faster than VLDLR and an LDLR-tail chimera; the paper also describes LRP as a clearance receptor. It does not test Aβ clearance or compare receptor performance at higher Aβ concentrations, so those parts of the claim remain unsupported. (LLM, conf=0.87)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“It has been shown that, at 5 nM, Aβ binding to LRP1 is not yet saturated (50,51).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
What the sources say
- Supportedcites [50] source
The Results report Aβ binding to LRP clusters with nonzero dissociation constants, including 0.57 and 1.24 nM for Aβ40 and higher values for other isoforms. These binding measurements support the inference that binding at 5 nM is not fully saturated, although the paper does not state that conclusion at 5 nM explicitly. (LLM, conf=0.84)
- Partly supportedcites [51] sourceExperimental — accuracy not yet measured
The binding-affinity passage (labeled Abstract in our copy; no page given) reports that Aβ40 and Aβ42 bind recombinant LRP cluster IV with dissociation constants of 1.9 and 5.1 nM, respectively. Those values are consistent with binding not being saturated at 5 nM, but the passage does not establish saturation at that concentration for intact LRP1. (LLM, conf=0.78)
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Full Lrp1 deletion was also confirmed via PCR analysis (26) on the genomic level (Figure 1C).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
What the sources say
- Supportedcites [26] Leneuve, 2001, Genotyping of Cre-lox mice and detection of tissue-specific recombination by multiplex PCR, Biotechniques source
The PCR Analysis of Cre-lox section reports using genomic PCR to detect complete recombination of a floxed locus in brain tissue. The citation supports PCR as a method for confirming genomic deletion; the Lrp1-specific result is the citing authors’ own finding, referenced to their Figure 1C. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
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Every source the paper cites for this claim was checked and supports it.
In the paper
“We detected that rapid BBB transport was reduced by about 48% in Lrp1 BE -/-mice (Figure 6C), whereas clearance through slow ISF bulk flow, a minor component of Aβ brain efflux (8), was not altered (Figure 6B).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
What the sources say
- Supportedcites [8] source
The citation is attached to the description of slow ISF bulk flow as a minor component of Aβ brain efflux, not to the citing authors’ 48% result in Lrp1 BE-/- mice. The Results (p. 4) report that ISF bulk flow accounted for 10.7% of Aβ1-40 efflux, compared with 73.8% via BBB transport. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, with an endocytosis rate up to 16 times faster than that of other Aβ receptors, such as VDLDR or LDLR (12,35), LRP1 may outperform other receptors in Aβ clearance, especially at higher concentrations.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
What the sources say
- Partly supportedcites [12] sourceExperimental — accuracy not yet measured
The Results report LRP1-mediated internalization with a half-time under 30 seconds, versus about 8.5 minutes through VLDLR. The Discussion describes VLDLR endocytosis as approximately 25-fold slower than LRP1, not a maximum of 16-fold, and the paper does not establish a comparable rate for LDLR; its Results say LDLR was not involved in uptake in the tested system. Page numbers are unavailable in our copy. (LLM, conf=0.86)
- Partly supportedcites [35] sourceExperimental — accuracy not yet measured
The Results report LRP internalization half-times below 30 seconds, versus over 8 minutes for VLDLR, supporting a substantial rate difference of at least 16-fold. The LDLR comparison used a receptor bearing the LDLR tail, not full-length LDLR, and our copy does not test Aβ internalization. The cited paper therefore does not establish the stated rate comparison for Aβ receptors specifically. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The clearance rate for inulin, k inulin , provides a measure of ISF flow, as inulin is neither transported across the BBB, nor retained in the brain (8).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Calculation of in vivo [ 125 I] Aβ 1-42 clearance.
What the sources say
- Supportedcites [8] source
The methods passage following Equation 1 (p. 3) explicitly states that inulin is neither transported across the BBB nor retained by the brain, and that its clearance rate, k_inulin, measures ISF bulk flow. The Results (p. 4) also describe inulin as a reference extracellular-fluid marker. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Additionally, in the 5xFAD mouse model of AD, brain endothelial-specific Lrp1 deletion reduced plasma Aβ levels and elevated soluble brain Aβ, leading to aggravated spatial learning and memory deficits, thus emphasizing the importance of systemic Aβ elimination via the BBB.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Selective deletion of Lrp1 in the brain endothelium of C57BL/6 mice strongly reduced brain efflux of injected [ 125 I] Aβ 1-42 .”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
boosteddirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Here, we developed transgenic mouse strains that allow for tamoxifen-inducible deletion of Lrp1 specifically within brain endothelial cells (Slco1c1-CreER T2 Lrp1 fl/fl mice) and used these mice to accurately evaluate LRP1-mediated Aβ BBB clearance in vivo.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In 7-month-old 5xFAD mice, we could not detect any significant differences in plaque deposition or gliosis when impairing a major Aβ elimination pathway through brain endothelial-specific deletion of Lrp1.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
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In the paper
“We found that at 5.14 nM [ 125 I] Aβ 1-42 , 47.5% of Aβ 1-42 BBB clearance was mediated by brain endothelial LRP1.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Again, there was a trend toward higher insoluble Aβ x-42 levels that did not reach statistical significance (Figure 7L).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
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In the paper
“Additionally, in the 5xFAD mouse model of AD, brain endothelial-specific Lrp1 deletion reduced plasma Aβ levels and elevated soluble brain Aβ, leading to aggravated spatial learning and memory deficits, thus emphasizing the importance of systemic Aβ elimination via the BBB.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Both calculations revealed that, at pathophysiological concentrations, about 27% of total Aβ 1-42 clearance is mediated by LRP1 in the brain endothelium, demonstrating the importance of systemic clearance across the BBB.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
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In the paper
“Additionally, the plasma Aβ 1-42 /Aβ 1-40 ratios in 5xFAD Lrp1 BE fl/fl animals were lowered by about the same fold (Figure 9).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Spatial learning tests in 5xFAD Lrp1 BE -/-mice after acquisition training showed significantly higher escape latencies on days 3, 4, and 5 compared with those of the rest of the groups (Figure 10A).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
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In the paper
“The knockout of Lrp1 is restricted to brain endothelium and choroid plexus epithelium.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Additionally, in the 5xFAD mouse model of AD, brain endothelial-specific Lrp1 deletion reduced plasma Aβ levels and elevated soluble brain Aβ, leading to aggravated spatial learning and memory deficits, thus emphasizing the importance of systemic Aβ elimination via the BBB.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Here, for what we believe to be the first time, a BBB-specific knockout mouse was used to evaluate the relevance of Aβ BBB clearance via LRP1.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition, the in vitro transport studies revealed a substantial contribution of LRP1 in Aβ transcytosis.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In order to clear about 70% of injected [ 125 I] Aβ 1-42 , mice lacking Lrp1 in brain endothelium needed about 4 times longer than control mice (Figure 6A, 60 minutes for Lrp1 BE -/-versus 15 minutes for Lrp1 BE fl/fl ), stressing the importance of endothelial LRP1 in rapid Aβ clearance.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Additionally, the results taken from the Aβ in vivo injection experiments in Lrp1 BE -/-mice are mirrored by these from the 5xFAD mice crossed into the Lrp1 BE -/-background.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the AD mouse model, we could observe similar effects.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
hedged- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that approximately 48% of BBB transport is mediated by LRP1.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, we observed the increasing contribution of LRP1 in receptor-mediated transcytosis of [ 125 I] Aβ 1-42 at rising Aβ concentrations.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Deletion of Lrp1 in brain endothelium results in reduced [ 125 I] Aβ 1-42 transcytosis in vitro.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Using physiological Aβ concentrations, we observed that half of the BBB clearance is mediated by brain endothelial LRP1 in various model systems.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, the vast majority of glial fibrillary acidic protein-positive (GFAPpositive) astrocytes in Lrp1 BE -/-mice were LRP1 positive (Figure 3B).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Therefore, brain endothelial LRP1mediated clearance accounted for approximately 27% of total Aβ 1-42 clearance (Figure 6F) at the Aβ concentration used in the study.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At all concentrations studied, we could verify our previous findings, showing that Lrp1 knockout endothelial cells transcytosed significantly less [ 125 I] Aβ 1-42 than control endothelial cells (Figure 5B).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Deletion of Lrp1 in brain endothelium results in reduced [ 125 I] Aβ 1-42 transcytosis in vitro.
hedgeddirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Precipitating brain radioactivity at designated time points after Aβ injection, we observed that at each time point Lrp1 BE -/-mice retained more [ 125 I] Aβ 1-42 than Lrp1 BE fl/fl mice (Figure 6A).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, we found no significant difference in Iba1 or GFAP immunoreactivity between 5xFAD Lrp1 BE -/-and 5xFAD Lrp1 BE fl/fl mice.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“LRP1 expression in neurons is not affected in this mouse model.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Plaque load quantification mirrored the data collected from prior measurements and showed no significant difference in plaque load in the hippocampus (Figure 7, J and K), cortex, or subiculum (Supplemental Figure 5).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We confirmed these findings in 5xFAD Lrp1 BE -/-mice in vivo.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, brain endothelial cells lacking LRP1 transcytosed approximately 50% less [ 125 I] Aβ 1-42 than brain endothelial cells isolated from littermate controls harboring the Lrp1 allele (Figure 5A).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Deletion of Lrp1 in brain endothelium results in reduced [ 125 I] Aβ 1-42 transcytosis in vitro.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Deletion of Lrp1 in Lrp1 BE -/-mice does not affect BBB integrity.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plainn = 8- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Spatial reference memory deficits in 5xFAD Lrp1 BE -/-mice were shown in the probe trial, in which 5xFAD Lrp1 BE -/-mice spent significantly less time in the target quadrant than all other groups of mice.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plaincorrelationaln = 5- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Quantification of Aβ x-40 and Aβ x-42 using ELISA showed (L) insoluble and (M) significantly elevated soluble Aβ x-40 and Aβ x-42 levels in 7-month-old 5xFAD Lrp1 BE -/-mice.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plainn = 10 ·- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“(B) Immunostaining in isolated endothelial cells showed knockout of Lrp1 in Lrp1 BE -/-mice.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“5xFAD Lrp1 BE fl/fl mice showed no impairment of spatial reference memory, as reflected by the significant greater percentage of time spent in the target quadrant (P < 0.001 target vs. left, right, and opposite quadrant).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plainn = 7- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Contribution of brain endothelial LRP1 to total and BBB clearance of 5.14 nM [ 125 I] Aβ 1-42 within 15 minutes”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plaindirectn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The fraction of Aβ remaining in the brain follows the two-compartment model N_b(Aβ)/N_i(Aβ) = (a1 + a2) × e^{-(k1+k2)t}, where k1 is total efflux and k2 is retention in the brain.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“(A) Brain IgG extravasation and (B) fluorescein permeability studies in Lrp1 BE fl/fl (n = 5) and Lrp1 BE -/-(n = 8) mice showed no effect of Lrp1 knockout on BBB permeability in vivo.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plainn = 8- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No difference in Lrp1 expression in capillary-depleted brain fractions of Lrp1 BE -/-and Lrp1 BE fl/fl mice.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plainn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Brain endothelial-specific deletion of Lrp1 in Lrp1 BE -/-mice.”
- Also stated in: § Spatial learning and spatial reference memory assessed by Morris water maze. · plain
“Immunofluorescent staining in cortical brain sections for LRP1 and (A) NeuN-positive neuronal cells, (B) GFAP-positive astrocytes, and (C) CD11b-positive microglia and macrophages to determine potential recombination in macrophages/microglia, neurons, and astrocytes revealed no differences between genotypes.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Spatial learning and spatial reference memory assessed by Morris water maze. · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Efflux across the BBB of 5.14 nM [ 125 I] Aβ 1-42 15 minutes after microinfusion in brain ISF demonstrated the substantial contribution of LRP1”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
boosteddirectn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The fraction of Aβ remaining in the brain follows the two-compartment model N_b(Aβ)/N_i(Aβ) = (a1 + a2) × e^{-(k1+k2)t}, where k1 is total efflux and k2 is retention in the brain.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A significant difference in the escape latency of 5xFAD Lrp1 BE -/-mice compared with that of all other groups was seen on days 3 to 5.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plaincorrelationaln = 5- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No alteration was observed in the bulk flow clearance of [ 14 C]-inulin”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plainn = 5- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No difference in astrogliosis and microgliosis due to brain endothelial knockout of LRP1 in 5xFAD mice.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plainn = 7- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“(C) PCR analysis revealed complete Cre-mediated excision of the loxP-flanked Lrp1 allele in brain endothelium.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Representative immunoprecipitations of (A) plasma Aβ, (B) soluble brain Aβ, and (C) insoluble brain Aβ, with 6E10 antibody from 7-month-old female mice show impaired brain-to-blood clearance of Aβ 1-40 and Aβ 1-42 .”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plaindirectn = 3 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The fraction of Aβ remaining in the brain follows the two-compartment model N_b(Aβ)/N_i(Aβ) = (a1 + a2) × e^{-(k1+k2)t}, where k1 is total efflux and k2 is retention in the brain.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Scarce presence of tracers in CSF 15 minutes after microinjection into the caudate nucleus”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Higher contribution of LRP1 in transport of [ 125 I] Aβ 1-42 at higher Aβ concentrations”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No effect on plaque deposition in hippocampus.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plainn = 7- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In senile plaques, LRP1 ligands, like apoE, urokinase-type plasminogen activator, tissue plasminogen activator, and lactoferrin, co-deposit with Aβ, all together indicating a loss of LRP1 function in AD (14).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
What the sources say
- Not checked — no full text of the sourcecites [14] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Additionally, highly validated genetic risk factors for AD, like the apolipoprotein E (apoE) Ε4 allele or the gene encoding the phosphatidylinositol-binding clathrin assembly (PICALM), are believed to be linked to reduced clearance of Aβ via LRP1 (11)(12)(13).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
What the sources say
- Not matchedcites (11)(12)(13)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Global Lrp1 knockout mice are embryonically lethal (22,23).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“5xFAD mice showed a preferential generation of Aβ 1-42 over Aβ 1-40 due to the mutations in amyloid precursor protein (APP) and presenilin-1 (37).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
What the sources say
- Not checked yetcites [37] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the 5xFAD model, these findings contradict the soluble Aβ accumulation that we observed in 5xFAD Lrp1 BE -/-mice.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Likewise, analysis of lysates revealed the absence of the protein in brain endothelial cells of Lrp1 BE -/-mice (Figure 1B).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Swimming speeds did not differ among groups (Figure 10B).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion, the data gathered with the brain endothelial-specific Lrp1 knockout mouse model prove that LRP1 in brain vasculature plays a key role in regulating brain Aβ levels.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This implicated that the low concentrations of Aβ injected into the caudate putamen were mostly eliminated by rapid clearance across the microvessels and not by clearance from the ISF into the CSF.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Tamoxifen injection into Lrp1 BE fl/fl mice carrying the Cre allele resulted in a full Lrp1 knockout in brain endothelium (herein referred to as Lrp1 BE -/-), as shown in immunohistochemical staining of cortical brain sections with monoclonal anti-LRP1 11E2 (Figure 1A and Supplemental Figures 2 and 3).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“As endothelial cells constitute only 1% to 2% of all cells in the brain (58), we do not believe that in 5xFAD Lrp1 BE -/-mice there is a significant effect on APP trafficking and overall Aβ production in the brain, compared with that in 5xFAD Lrp1 BE fl/fl mice.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
What the sources say
- Not checked — no full text of the sourcecites [58] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We could not see any effects on the in vivo BBB permeability due to the knockout of Lrp1 in endothelial cells.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Neither with the monoclonal N-terminal 11E2 (Supplemental Figure 2) nor with the well-described polyclonal C-terminal antibody 1704 could we see differences in Lrp1 expression in brain tissue deprived of capillaries (Figure 2).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Tamoxifen injection in WT mice did not affect Lrp1 expression (Supplemental Figure 1; supplemental material available online with this article; doi:10.1172/JCI81108DS1).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that spatial learning is impaired in 5xFAD Lrp1 BE -/-mice.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We used three different tests to examine motor deficits, string suspension, inverted grip, and balance beam, and found that no mice in any tested group showed abnormalities (Supplemental Figure 6).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The paracellular marker [ 14 C]-inulin was cleared in a slow, passive, and equal manner in both groups, demonstrating an intact BBB (Figure 6B).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The data furthermore suggest that, at elevated Aβ concentrations, like during the progression of AD, the importance of Aβ clearance by fast endocytic receptor LRP1 is crucial.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggested that approximately 44% of the low nM Aβ pool in mice still present after 3 hours could only be cleared when LRP1 was present in brain endothelium.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, our results suggest that receptor-mediated Aβ BBB clearance may be a potential target for treatment and prevention of Aβ brain accumulation in AD.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: unclear — It is unclear whether it could be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“As endothelial cells constitute only 1% to 2% of all cells in the brain (58), we do not believe that in 5xFAD Lrp1 BE -/-mice there is a significant effect on APP trafficking and overall Aβ production in the brain, compared with that in 5xFAD Lrp1 BE fl/fl mice.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
What the sources say
- Not checked — no full text of the sourcecites [58] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“This demonstrated that LRP1, with an extremely fast endocytosis rate (35), has a major function as an Aβ clearance receptor in endothelial cells.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Deletion of Lrp1 in brain endothelium results in reduced [ 125 I] Aβ 1-42 transcytosis in vitro.
What the sources say
- Not checked yetcites [35] source
Checked before — its earlier verdict is held back until a new check runs.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not checked yet
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here, in the two BBB-specific knockout mouse models of Lrp1, we can positively say that the expression of LRP1 in brain endothelial cells strongly modulates soluble brain Aβ levels.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Brain endothelial LRP1 substantially mediates Aβ clearance in vivo.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plaindirectn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The fraction of Aβ remaining in the brain follows the two-compartment model N_b(Aβ)/N_i(Aβ) = (a1 + a2) × e^{-(k1+k2)t}, where k1 is total efflux and k2 is retention in the brain.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“BBB clearance of Aβ species in 5xFAD mice is regulated by brain endothelial LRP1.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plaindirectn = 5 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The fraction of Aβ remaining in the brain follows the two-compartment model N_b(Aβ)/N_i(Aβ) = (a1 + a2) × e^{-(k1+k2)t}, where k1 is total efflux and k2 is retention in the brain.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Deletion of Lrp1 in brain endothelial cells leads to cognitive deficits in 5xFAD Lrp1 BE -/-mice.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plaindirectn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Preferential clearance of Aβ 1-40 species by brain endothelial LRP1.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plaindirectn = 6 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The fraction of Aβ remaining in the brain follows the two-compartment model N_b(Aβ)/N_i(Aβ) = (a1 + a2) × e^{-(k1+k2)t}, where k1 is total efflux and k2 is retention in the brain.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“LRP1 in brain endothelial cells substantially contributes to [ 125 I] Aβ 1-42 transcytosis in vitro.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plaindirectn = 18- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 22
- It may state two separate claims as one. 41
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Thus, the neurovascular hypothesis of AD states that Aβ accumulation is driven by impairment of Aβ transporters in brain capillaries, resulting in deficient Aβ elimination via the BBB (3,8,15,16).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Supportedcites [8] source
The conclusion (Figure 7, p. 10) says impaired vascular transport across the BBB, for example through LRP-1 downregulation, would result in brain Aβ accumulation. The Discussion (p. 7) identifies LRP-1 in brain microvascular endothelium as a principal mediator of this clearance, supporting the claim as a statement of the hypothesis. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [15] Deane, 2004, RAGE (yin) versus LRP (yang) balance regulates alzheimer amyloid beta-peptide clearance through transport across the blood-brain barrier, Stroke source
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Introduction identifies BBB transporters involved in Aβ movement, and the Discussion reports that Aβ transport across the BBB is disrupted in transgenic mouse models of AD. The paper does not establish that impaired transporters in brain capillaries drive Aβ accumulation in AD, as the citing sentence states. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Cell-surface receptor low-density lipoprotein receptor-related protein-1 (LRP1) has been reported to be involved not only in Aβ endocytosis and cerebral degradation (5)(6)(7), but also in Aβ transcytosis through the brain endothelium and subsequent systemic elimination via liver, spleen, and kidneys (8).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
What the sources say
- Not matchedcites (5)(6)(7)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites [8] sourceExperimental — accuracy not yet measured
The Discussion (p. 7) says that LRP-1 in brain microvascular endothelium mainly mediates Aβ transport across the blood-brain barrier into circulation. The passage following Figure 6 (p. 8) also discusses systemic metabolism and body clearance, but our copy does not identify the liver, spleen, and kidneys as the sites of that elimination. (LLM, conf=0.86)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Low Aβ levels within the healthy brain are maintained through degradation, elimination via interstitial fluid (ISF) bulk flow, cerebrospinal fluid (CSF) absorption into the circulatory and lymphatic system, or transport across the blood-brain barrier (BBB) (3,4).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Supportedcites [4] source
The Introduction lists degradation, ISF bulk flow, CSF absorption into the circulatory and lymphatic systems, and transport across the BBB as routes for removing soluble Aβ from the brain. These are the routes attributed to the source in the citing sentence. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Due to the lack of appropriate model systems, the role of LRP1 at the BBB and the overall relevance of BBB clearance are insufficiently understood and debated (4,7).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
What the sources say
- Partly supportedcites [4] sourceExperimental — accuracy not yet measured
The ‘Blood-brain barrier clearance’ section reports conflicting findings on whether LRP1 is a major or minor transporter for Aβ efflux. The ‘Clearance systems’ section says the relative contributions of clearance routes are unknown and that newer studies challenge the prevailing view that BBB clearance predominates. The paper does not attribute these uncertainties to a lack of appropriate model systems. (LLM, conf=0.85)
- Partly supportedcites [7] sourceExperimental — accuracy not yet measured
The Introduction says endothelial LRP1’s role in Aβ transcytosis across the BBB remains controversial, and the Discussion says there is no direct in vivo evidence that it controls Aβ elimination at the BBB. The paper also questions whether this is a significant brain Aβ-clearance pathway. It does not attribute those uncertainties to a lack of appropriate model systems. Page numbers are unavailable in our copy. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Many Aβ clearance studies make use of LRP1 inhibition through injected antibodies or low-density lipoprotein receptor (LDLR) family antagonists; however, this approach does not allow the specific inhibition of the BBB clearance pathway (21).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
What the sources say
- Partly supportedcites [21] sourceExperimental — accuracy not yet measured
The Discussion (page not available) reports that intracerebral RAP inhibition reduced both Aβ40 clearance across the BBB and degradation in the brain, supporting the concern that this intervention does not isolate the BBB clearance pathway. It mentions a prior study using an LRP1 antibody, but does not establish that many studies use injected antibodies or that antibody inhibition has the same limitation. (LLM, conf=0.82)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“When injecting low nM [ 125 I] Aβ 1-42 concentrations in mice, we found no significant amount of radioactivity in the CSF, showing that the small amounts of injected Aβ are rapidly cleared via the BBB and that a minor amount of injected Aβ is cleared via bulk flow as also observed by previous studies (8,11,12).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
What the sources say
- Partly supportedcites [8] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Supportedcites [11] Bell, 2007, Transport pathways for clearance of human Alzheimer’s amyloid β-peptide and apolipoproteins E and J in the mouse central nervous system, J Cereb Blood Flow Metab source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [12] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The binding affinity results, as well as the predominant importance of LRP1 at elevated Aβ concentrations, support the idea that maintaining steady Aβ clearance at the BBB by LRP1 could be a potential target for treatment of agerelated neurological disorders (51).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
What the sources say
- Partly supportedcites [51] sourceExperimental — accuracy not yet measured
The Abstract reports high-affinity Aβ binding by LRP-IV and describes LRP1-mediated Aβ clearance at the BBB. It proposes LRP-IV as a peripheral Aβ-clearance therapy for Alzheimer’s disease, but does not establish that BBB LRP1 is predominantly important at elevated Aβ concentrations or propose maintaining its BBB activity to treat age-related neurological disorders generally. (LLM, conf=0.86)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Previous studies have shown higher binding affinity of LRP1 to Aβ 1-40 and faster clearance of this variant than of Aβ 1-42 (11,15).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
What the sources say
- Partly supportedcites [11] Bell, 2007, Transport pathways for clearance of human Alzheimer’s amyloid β-peptide and apolipoproteins E and J in the mouse central nervous system, J Cereb Blood Flow Metab sourceExperimental — accuracy not yet measured
The Discussion reports that Aβ42 is cleared across the blood–brain barrier 1.9-fold more slowly than Aβ40, and the Results identify LRP1-dependent efflux of both peptides. The paper does not report that LRP1 has a higher binding affinity for Aβ40 than for Aβ42. Page numbers are unavailable in our copy. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [15] Deane, 2004, RAGE (yin) versus LRP (yang) balance regulates alzheimer amyloid beta-peptide clearance through transport across the blood-brain barrier, Stroke source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“It has been shown that LRP1 is required for APP trafficking and Aβ production.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
What the sources say
- Partly supportedcites [57] sourceExperimental — accuracy not yet measured
The Discussion reports that blocking LRP reduced Aβ secretion and increased cell-surface APP; the results also report that restoring LRP increased Aβ production. But the paper proposes, rather than demonstrates, that LRP alters APP trafficking, and describes reduced—not absent—Aβ production without LRP activity. It therefore does not establish that LRP1 is required for both processes. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Cell-specific functions of receptors have been reported for other members of the LDLR family (53), so the function of LRP1 might be dependent on cell type and polarization state, as suggested before (21,32).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
What the sources say
- Not checked — no full text of the sourcecites [53] source
- Supportedcites [21] source
The Discussion states that conflicting findings suggest LRP1 mediates Aβ40 endocytosis or transcytosis depending on cell type and polarization state. This supports the qualified LRP1 claim attached to citations (21,32); the preceding claim about other LDLR-family members is attached to citation (53). (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [32] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“When LRP1 expression decreases during aging and in AD (8, 10), fewer receptors will not only cause rising Aβ accumulation in the brain, but will preferentially clear less toxic Aβ 1-40 and therefore cause a shift in the Aβ 1-42 /Aβ 1-40 ratio, leading to higher concentrations of aggregation-prone Aβ 1-42 .”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
What the sources say
- Partly supportedcites [8] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [10] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Previously, it has been shown that 5xFAD mice display AD-like memory deficits at 12 months of age (43).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
What the sources say
- Supportedcites [43] Bouter, 2014, Deciphering the molecular profile of plaques, memory decline and neuron loss in two mouse models for Alzheimer’s disease by deep sequencing, Front Aging Neurosci source
The Results section on contextual learning reports that 12-month-old 5XFAD mice showed impaired contextual fear learning compared with wild-type mice (page unavailable). The Results section on tone learning also reports impaired conditioning in 5XFAD mice at 12 months, supporting the claim of AD-like memory deficits. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Inhibition of LRP1 in cultured cells has been shown to significant reduce Aβ production (57).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
What the sources say
- Supportedcites [57] source
The section “Cells Cultured in the Presence of RAP Produce Less Aβ Than Control Cells” describes RAP as an LRP antagonist and reports that prolonged treatment of cultured cells significantly decreased Aβ production. The Discussion likewise reports a significant reduction in Aβ secreted into the medium. (LLM, conf=0.94)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These results might be due to Aβ injections at concentrations beyond physiological relevance into different brain regions (17, 18, 52) or the use of epithelial cells, such as MDCK and CHO cells (5,19), for in vitro studies.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
What the sources say
- Not checked — no full text of the sourcecites [17] Ito, 2010, Lack of brain-to-blood efflux transport activity of low-density lipoprotein receptor-related protein-1 (LRP-1) for amyloid-β peptide(1-40) in mouse: involvement of an LRP-1-independent pathway, J Neurochem source
- Partly supportedcites [18] Ito, 2007, Cerebral clearance of human amyloid-beta peptide (1-40) across the blood-brain barrier is reduced by self-aggregation and formation of low-density lipoprotein receptor-related protein-1 ligand complexes, J Neurochem sourceExperimental — accuracy not yet measured
The Discussion (page not specified in our copy) suggests that conflicting LRP-1 findings might reflect differences in where and how Aβ was injected into the brain. It does not say that the injected concentrations exceeded physiological levels. The MDCK/CHO-cell point is attached to different citations in the citing sentence, so it is not assessed against this source. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [52] Ito, 2006, Functional characterization of the brain-to-blood efflux clearance of human amyloid-β peptide (1-40) across the rat blood-brain barrier, Neurosci Res source
- Supportedcites [5] source
The Results state that the paper’s MDCK monolayer is not of endothelial origin, and the Discussion explicitly describes its principal in vitro MDCK model as epithelial. This supports the MDCK example for which this source is cited; the injection and CHO-cell examples have separate citations. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [19] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Although there are additional methods of Aβ clearance (6, 7, 38, 39), our and other data show that vascular transport across the BBB is of crucial importance for rapid Aβ elimination from brain (8,11,15).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
What the sources say
- Supportedcites [6] source
This source supports the sentence’s opening point that Aβ has additional clearance routes, rather than the later claim about rapid transport across the BBB, which carries a separate citation group. The Discussion (page unavailable) reports neuronal LRP1-mediated Aβ uptake and degradation, and also describes clearance by astrocytes, microglia, and vascular smooth muscle cells. (LLM, conf=0.90)
- Partly supportedcites [7] sourceExperimental — accuracy not yet measured
The Abstract describes cerebrovascular clearance as a major pathway and says Aβ can be eliminated through the BBB, while the Discussion acknowledges other clearance pathways. But the Abstract says whether BBB transcytosis is a significant clearance pathway remains controversial; this paper demonstrates local clearance by vascular smooth muscle cells, not that transport across the BBB is crucial for rapid elimination. The indexed passages provide no page numbers. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [38] source
- Not checked — no full text of the sourcecites [39] source
- Supportedcites [8] source
The discussion (p. 9) acknowledges other possible routes of Aβ clearance but says vascular transport across the BBB appears to be of primary importance for rapid elimination from the brain in vivo. The discussion (p. 7) also identifies BBB transport as the major component of Aβ efflux in the study. (LLM, conf=0.95)
- Supportedcites [11] Bell, 2007, Transport pathways for clearance of human Alzheimer’s amyloid β-peptide and apolipoproteins E and J in the mouse central nervous system, J Cereb Blood Flow Metab source
The Results report that BBB transport is a major efflux route for Aβ40 from the mouse CNS, with an efflux rate more than sixfold greater than transport via interstitial-fluid flow. The Introduction also describes other clearance mechanisms, matching the claim’s qualification. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [15] Deane, 2004, RAGE (yin) versus LRP (yang) balance regulates alzheimer amyloid beta-peptide clearance through transport across the blood-brain barrier, Stroke source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Before injection of tracer molecules, animals recovered for 4 to 6 hours, a time point that precedes the start of the substantial inflammatory process, as assessed by histological analysis of tissue (negative staining for reactive astrocytes [GFAP] and reactive microglia [antiphosphotyrosine]), but allows partial BBB repair for large molecules, as reported previously (15,61).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > C].
What the sources say
- Not checked — no full text of the sourcecites [15] Deane, 2004, RAGE (yin) versus LRP (yang) balance regulates alzheimer amyloid beta-peptide clearance through transport across the blood-brain barrier, Stroke source
- Partly supportedcites [61] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition, Aβ can be retained in the brain by binding to transport proteins or cell-surface receptors (8).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Immunoprecipitation of Aβ.
What the sources say
- Supportedcites [8] source
In the model description (p. 3), the paper explicitly says Aβ may be retained in the brain by binding to cell-surface receptors or transport proteins. This matches the citing sentence’s qualified claim that it can be retained that way. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Spatial reference memory in 5xFAD Lrp1 BE -/-mice and 5xFAD Lrp1 BE fl/fl control mice was assessed using the Morris water maze (40) by a blinded investigator as described previously (41).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
What the sources say
- Not checked — no full text of the sourcecites [40] source
- Partly supportedcites [41] sourceExperimental — accuracy not yet measured
The Materials and methods section (‘Spatial reference memory by Morris water maze’; page unavailable) describes using the maze to assess spatial reference memory, supporting the citation as a prior method. It reports testing Tg4-42 mice, not the citing study’s 5xFAD Lrp1 groups, and does not state that the investigator was blinded. The latter detail is therefore not supported by this source. (LLM, conf=0.84)
plainn = 7- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Within the first 20 minutes, Aβ was cleared in a linear manner, with 47.7% more clearance in Lrp1 BE fl/fl mice studied 15 minutes after injection (Figure 6A).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Insoluble Aβ 1-42 levels showed a trend toward higher levels in 5xFAD Lrp1 BE -/-mice, with higher variations in individual mice (Figure 7, C, H, and I).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, absence of LRP1 in brain endothelium had striking effects on the concentrations of soluble Aβ species in the brain and resulted in significant cognitive deficits.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both AD models showed reactive astrocytes and microglia in the hippocampus (Figure 8).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Soluble Aβ levels were elevated about 2.5-fold for Aβ 1-42 and about 3.7-fold for Aβ 1-40 in 5xFAD Lrp1 BE -/-mice.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When measuring the Aβ 1-42 /Aβ 1-40 ratio in 5xFAD mice, we saw that both Aβ variants were cleared by LRP1 but noticed preferential clearance of Aβ 1-40 .”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Reflecting the immunoprecipitation data, 7-month-old 5xFAD mice had significantly higher soluble Aβ levels (approximately 4.8-fold for Aβ x-40 and 3.1-fold for Aβ x-42 ) and insoluble Aβ x-40 levels (approximately 2.0-fold change) when LRP1 was absent in brain endothelium (Figure 7, L and M).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“While, at picomolar concentrations, the contribution of LRP1-mediated clearance was 49.2% (0.1 nM Aβ), it increased with rising Aβ concentrations to 65.4% at 5 nM Aβ.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, 30 minutes after CNS injection, Aβ brain retention in both groups approximated a respective plateau, with reduction (about 44%) of Aβ brain retention in brains of Lrp1 BE fl/fl animals, even 3 hours after injection of these small amounts of tracers (Figure 6A).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In 7-month-old 5xFAD Lrp1 BE -/-animals, the plasma levels for both Aβ 1-40 and Aβ 1-42 are strongly reduced and the brain levels highly elevated, each by more than 50%.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“5xFAD Lrp1 BE -/mice showed reduced plasma levels of both Aβ 1-40 and Aβ 1-42 associated with reduced Aβ transport out of the brain (Figure 7, A, D, and E).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In vivo, plasma Aβ levels in 5xFAD mice were significantly reduced and soluble brain levels were significantly elevated when LRP1 was absent in brain jci.org endothelium.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In 7-month-old 5xFAD Lrp1 BE fl/fl animals, both soluble and insoluble Aβ 1-42 /Aβ 1- 40 brain ratios were significantly elevated (Figure 9), suggesting that LRP1 preferentially clears Aβ 1-40 , even when Aβ 1-42 is of higher abundance.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In line with these data, we found significantly higher levels of soluble Aβ in 5xFAD Lrp1 BE -/-brains, consistent with impaired transport of Aβ out of the brain (Figure 7, B, F, and G).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Deleting Lrp1 in brain endothelium severely increased soluble Aβ levels and elevated the Aβ 1-42 /Aβ 1-40 ratio.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“(A) Immunofluorescent staining for endothelial marker CD31 and LRP1 in cortical brain sections demonstrated complete knockout of Lrp1 in brain endothelium of Lrp1 BE -/-animals, while Lrp1 expression in surrounding cells remained unaffected (white arrows).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The probe trial revealed a significant impairment of spatial reference memory in 5xFAD Lrp1 BE -/-mice, as they showed no preference for the target quadrant.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plainn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Swimming speed was not affected in all mice tested.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Densitometry analysis of immunoprecipitated soluble brain Aβ, insoluble brain Aβ, and plasma Aβ with 6E10 antibody from 7-month-old mice (n = 3, n = 5, n = 7, n = 6, n = 3, n = 3 from left to right) showed higher Aβ 1-40 and Aβ 1-42 /Aβ 1-40 ratios in plasma and lower and Aβ 1-42 /Aβ 1-40 ratios in brain fractions when LRP1 is present in brain endothelial cells.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
plaincorrelationaln = 6 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: The fraction of Aβ remaining in the brain follows the two-compartment model N_b(Aβ)/N_i(Aβ) = (a1 + a2) × e^{-(k1+k2)t}, where k1 is total efflux and k2 is retention in the brain.
In the paper
“The two additional hydrophobic amino acids of Aβ 1-42 generate a more aggregation-prone and neurotoxic peptide (2).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
What the sources say
- Not checked — no full text of the sourcecites [2] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“However, there are conflicting studies showing no or little contribution of LRP1 to Aβ clearance across the BBB (5,(17)(18)(19)(20).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
What the sources say
- Not matchedcites (5,(17)(18)(19)(20)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This led to severe effects on cognitive function, supporting the idea that soluble Aβ, but not plaque-bound Aβ, correlates with AD-related symptoms.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Deletion of Lrp1 in brain endothelium in an AD mouse model enhances Aβ accumulation and leads to AD-related behavioral deficits.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In AD, activated astrocytes and microglia play an important role in clearing Aβ deposits by triggering phagocytic uptake (38,39).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Brain permeability for IgG and the low-molecular-weight marker Na-fluorescein did not show differences between genotypes, indicating an intact BBB in vivo (Figure 4).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Introduction
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, both tracers were hardly detectable in CSF, with no differences among the groups (Figure 6, D and E).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This binding affinity difference could lead to fatal consequences in patients.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
In the paper
“In their study with 19 patients with AD and 18 controls, McLean and colleagues discovered that insoluble Aβ in humans appeared only to signify the presence of AD and that soluble Aβ concentrations seemed to correlate with the severity of disease.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
What the sources say
- Not checked — no full text of the sourcecites [55] source
hedgedcorrelationaln = 19- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All together, the collected data from two different in vivo models indicated that brain endothelial LRP1 substantially regulates the soluble brain Aβ levels and that LRP1-mediated transport across the BBB is a major pathway of Aβ clearance.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This demonstrates that LRP1 preferentially binds Aβ 1-40 when available, confirming previous findings showing a differential affinity of LRP1 to the two Aβ variants (15).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
What the sources say
- Not checked — no full text of the sourcecites [15] Deane, 2004, RAGE (yin) versus LRP (yang) balance regulates alzheimer amyloid beta-peptide clearance through transport across the blood-brain barrier, Stroke source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, the results illustrated that endothelial-specific Lrp1 knockout in 5xFAD mice and, therefore, reduced clearance of Aβ peptides induced an impairment of both spatial learning and spatial reference memory.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, their data on patients with AD showed a higher proportion of Aβ 1-42 in the soluble fractions, possibly representing an intracellular and more neurotoxic pool of Aβ (55).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
What the sources say
- Not checked — no full text of the sourcecites [55] source
hedgedcorrelationaln = 19- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“As recent works suggest, the concentrations of soluble Aβ species, not the presence of plaques, seem to strongly correlate with the cognitive deficits in mouse models (54) and AD pathology in patients (55,56).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
What the sources say
- Not checked — no full text of the sourcecites [54] Dodart, 2002, Immunization reverses memory deficits without reducing brain Aβ burden in Alzheimer’s disease model, Nat Neurosci source
- Not checked — no full text of the sourcecites [55] source
- Not checked yetcites [56] Mc Donald, 2010, The presence of sodium dodecyl sulphate-stable Aβ dimers is strongly associated with Alzheimer-type dementia, Brain source
Checked before — its earlier verdict is held back until a new check runs.
hedgedcorrelationaln = 19- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A closer look at the vasculature revealed that CD31-negative cells adjacent to the endothelium that make up the neurovascular unit were positive for LRP1 in Lrp1 BE -/-mice (Figure 1A and Supplemental Figure 3), showing brain endothelial-specific expression of Cre recombinase and no leakage of Cre recombinase in surrounding cells.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Slco1c1-CreER T2 × Lrp1 fl/fl mice fully excise Lrp1 specifically in brain endothelium.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The levels of Aβ x-40 and Aβ x-42 peptides in brain extractions were blindly determined using a cell-based sandwich ELISA assay as described previously (63).”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain IgG extravasation.
What the sources say
- Not checked — no full text of the sourcecites [63] Hahn, 2011, Presenilin-1 but not amyloid precursor protein mutations present in mouse models of Alzheimer’s disease attenuate the response of cultured cells to γ-secretase modulators regardless of their potency and structure, J Neurochem source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Total Aβ was immunoprecipitated from blinded samples of blood serum and soluble and insoluble brain pools by mixing 5-fold concentrated detergent buffer (50 mM HEPES [pH 7.4], 150 mM NaCl, 0.5 % [v/v] Nonidet P-40, 0.05% [w/v] SDS and protease inhibitor cocktail [Roche Applied Science]) with the respective samples.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Immunoprecipitation of Aβ.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“The ability of vision of the mice was tested by visual placing (42) before mice entered the Morris water maze.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
What the sources say
- Not checked — no full text of the sourcecites [42] Heyser, 2004, Assessment of developmental milestones in rodents, Curr Protoc Neurosci source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Blinded brain samples were collected at different time points and prepared for analysis.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > C].
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As LRP1 levels decrease with aging and in AD, maintaining the function of Aβ transporters could be a potential strategy for treatment and prevention of AD.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.
The paper relies on this without support.
No animal model had been available to study the role of LRP1 at the BBB.
“Until now, no animal model had been available to study the role of LRP1 at the BBB.”
The paper relies on this without support.
Much of the Aβ in the brain is produced by neurons in which there is both high APP and LRP1 expression.
“However, much of the Aβ in the brain is produced by neurons in which there is both high APP and LRP1 expression.”
The authors state this as an assumption.
The role of Aβ production in this paradigm is minimal.
“Therefore, we assume that the role of Aβ production in this paradigm is minimal.”
The authors state this as an assumption.
The fraction of Aβ remaining in the brain follows the two-compartment model N_b(Aβ)/N_i(Aβ) = (a1 + a2) × e^{-(k1+k2)t}, where k1 is total efflux and k2 is retention in the brain.
“According to our model, the fraction of Aβ remaining in the brain can be expressed as follows: N b(Aβ) /N i(Aβ) = (a 1 + a 2 ) × e -(k1+k2) × t , where a 1 = k 2 /(k 1 +k 2 ), a 2 = (1 -(k 2 /(k 1 + k 2 ))), k 1 signifies the total efflux, and k 2 represents the retention in the brain.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Approximately 85% of A β is eliminated via BBB-mediated efflux [ 16 ], primarily through low-density lipoprotein receptor-related protein 1 (LRP1), expressed on cerebrovascular endothelial cells [ 15-17 ].”
From Restores Aβ Clearance by Overcoming PCSK9–LRP1 Dysregulation and TRIB3‐Mediated Autophagy Blockade in Alzheimer's Disease (2026) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Thus, endothelial expression of LRP1 promotes the clearance of Aβ across the BBB in vivo, a process directly modulated by PCSK9 inhibitor treatment (93, 94), and the expression of CD36 parallels the ability of microglia to perform Aβ clearance (95).”
From PCSK9 and the nervous system: a no-brainer? (2023) · cites this paper as [93]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Proprotein convertase subtilisin/kexin type 9 (PCSK9) negatively regulates low-density lipoprotein receptor family members, including low-density lipoprotein receptor -related protein 1 (LRP1), a key mediator of blood-brain barrier (BBB) Aβ efflux”
From Small-molecule PCSK9 inhibition enhances BBB amyloid-β clearance and suppresses microglial inflammation in Alzheimer’s disease models (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Concerning LRP1, it regulates Aβ efflux through the BBB and in addition its expression in the whole brain and brain capillaries appeared reduced with ageing and in AD, negatively impacting soluble Aβ clearance and leading to amyloid deposition [39,85,86,87].”
From The Emerging Role of PCSK9 in the Pathogenesis of Alzheimer’s Disease: A Possible Target for the Disease Treatment (2024) · cites this paper as [39]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Aβ peptides have been reported to directly bind LRP1 for clearance37,38.”
From Brain-targeted drug delivery by manipulating protein corona functions (2019) · cites this paper as [38]
The cited source says what the claim attributes to it.
In the citing paper
“If LRP1is similarly downregulated in PD as in AD (137, 561), this could result in impaired 𝛂 -syn BBB clearance and accumulation of 𝛂 -syn in brain.”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [561]
The cited source says what the claim attributes to it.
In the citing paper
“The brain-to-blood transfer of monomeric Aβ is highly dependent on low-density lipoprotein receptor-related protein 1 (LRP1) [13, 14], which in brain endothelium is primarily located at the abluminal side [13, 15].”
From PCSK9 acts as a key regulator of Aβ clearance across the blood–brain barrier (2022) · cites this paper as [14]
The cited source says what the claim attributes to it.
In the citing paper
“LRP1 is a key mediator of cerebral Aβ clearance by its rapid Aβ transport across the BBB into the periphery [13, 14].”
From PCSK9 acts as a key regulator of Aβ clearance across the blood–brain barrier (2022) · cites this paper as [14]
The cited source says what the claim attributes to it.
In the citing paper
“Among clearance pathways, LRP1 plays a dominant role in mediating BBB Aβ efflux, and reduced LRP1 availability markedly compromises this process24.”
From Small-molecule PCSK9 inhibition enhances BBB amyloid-β clearance and suppresses microglial inflammation in Alzheimer’s disease models (2026) · cites this paper as [24]
The cited source says what the claim attributes to it.
In the citing paper
“This effect is consistent with the established role of endothelial LRP1 as a major mediator of BBB Aβ clearance24”
From Small-molecule PCSK9 inhibition enhances BBB amyloid-β clearance and suppresses microglial inflammation in Alzheimer’s disease models (2026) · cites this paper as [24]
The cited source says what the claim attributes to it.
In the citing paper
“The lack of effect on blood-to-brain-like transport is consistent with the established directionality of LRP1-mediated Aβ clearance24.”
From Small-molecule PCSK9 inhibition enhances BBB amyloid-β clearance and suppresses microglial inflammation in Alzheimer’s disease models (2026) · cites this paper as [24]
The cited source says what the claim attributes to it.
In the citing paper
“LRP1 on endothelial cells of the blood-brain barrier mediates export of Aβ out of the brain (27)”
From LRPAP1 is released from activated microglia and inhibits microglial phagocytosis and amyloid beta aggregation (2023) · cites this paper as [27]
The cited source says what the claim attributes to it.
In the citing paper
“Cellular receptors such as low-density lipoprotein receptor-related protein 1 (LRP1) [47–50], LRP8 [51], LDLR [52] or RAGE [53] may also affect APP metabolism by either modulating the activities of β- and γ-secretase and/or directly Aβ levels through endocytosis.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Brain endothelial LRP1 deficiency exacerbates Aβ-dependent cognitive deficits.
“Soluble Aβ levels were elevated about 2.5-fold for Aβ 1-42 and about 3.7-fold for Aβ 1-40 in 5xFAD Lrp1 BE -/-mice.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > jci.org
“Deleting Lrp1 in brain endothelium severely increased soluble Aβ levels and elevated the Aβ 1-42 /Aβ 1-40 ratio.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
“7-month-old female 5xFAD Lrp1 BE -/-(n = 7), 5xFAD Lrp1 BE fl/fl (n = 7), Lrp1 BE -/-(n = 5), and WT (n = 6) control mice were tested.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
“7-month-old female 5xFAD Lrp1 BE -/-(n = 5), 5xFAD Lrp1 BE fl/fl (n = 7), Lrp1 BE -/-(n = 5), and WT (n = 6) control mice were tested.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > Spatial learning and spatial reference memory assessed by Morris water maze.
“(A) 5.14 nM [ 125 I] Aβ 1-42 and 40 μCi/ml [ 14 C]-inulin, a paracellular marker, were microinfused into brain ISF of the caudate nucleus.”
§ Endothelial LRP1 transports amyloid-β 1-42 across the blood-brain barrier > C].
“0.5 μl tracer fluid containing 1 μCi/ml [ 14 C]-inulin (reference marker) and physiological amounts of [ 125 I] Aβ 1-42 (5.14 nM) was injected”
Citations
Cites
Developments of a water-maze procedure for studying spatial learning in the rat
Morris, R. (1984) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(84)90007-4 · Cited by 7,180
Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530 · cited 7×
“Functional characterization of the brain-to-blood efflux clearance of human amyloid-β peptide (1-40) across the rat blood-brain barrier.”
InfluentialNeurovascular regulation in the normal brain and in Alzheimer's disease
Iadecola, C. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1387 · Cited by 2,213
Decreased Clearance of CNS β-Amyloid in Alzheimer’s Disease
Mawuenyega, K. G., Sigurdson, W., Ovod, V., Munsell, L., Kasten, T., Morris, J. C., Yarasheski, K. E., & Bateman, R. J. (2010) · Science · doi:10.1126/science.1197623 · Cited by 2,078
Clearance systems in the brain—implications for Alzheimer disease
Tarasoff-Conway, J. M., Carare, R. O., Osorio, R. S., Glodzik, L., Butler, T., Fieremans, E., Axel, L., Rusinek, H., Nicholson, C., Zlokovic, B. V., et al. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.119 · Cited by 1,678
Shibata, M., Yamada, S., Kumar, S. R., Calero, M., Bading, J., Frangione, B., Holtzman, D. M., Miller, C. A., Strickland, D. K., Ghiso, J., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10498 · Cited by 1,413
Adult mouse astrocytes degrade amyloid-β in vitro and in situ
Wyss-Coray, T., Loike, J. D., Brionne, T. C., Lu, E., Anankov, R., Yan, F., Silverstein, S. C., & Husemann, J. (2003) · Nature Medicine · doi:10.1038/nm838 · Cited by 909
Immunization reverses memory deficits without reducing brain Aβ burden in Alzheimer's disease model
Dodart, J.-C., Bales, K. R., Gannon, K. S., Greene, S. J., DeMattos, R. B., Mathis, C., DeLong, C. A., Wu, S., Wu, X., Holtzman, D. M., et al. (2002) · Nature Neuroscience · doi:10.1038/nn842 · Cited by 858
Alzheimer Disease as a Vascular Disorder
de la Torre, J. C. (2002) · Stroke · doi:10.1161/01.str.0000014421.15948.67 · Cited by 852
LRP/Amyloid β-Peptide Interaction Mediates Differential Brain Efflux of Aβ Isoforms
Deane, R., Wu, Z., Sagare, A., Davis, J., Du Yan, S., Hamm, K., Xu, F., Parisi, M., LaRue, B., Hu, H. W., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.07.017 · Cited by 828
Cited by
Sorted by citations
Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.188 · Cited by 3,076
Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,312
Multi-sensory Gamma Stimulation Ameliorates Alzheimer’s-Associated Pathology and Improves Cognition
Martorell, A. J., Paulson, A. L., Suk, H.-J., Abdurrob, F., Drummond, G. T., Guan, W., Young, J. Z., Kim, D. N.-W., Kritskiy, O., Barker, S. J., et al. (2019) · Cell · doi:10.1016/j.cell.2019.02.014 · Cited by 798
The blood–brain barrier in health and disease: Important unanswered questions
Profaci, C. P., Munji, R. N., Pulido, R. S., & Daneman, R. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20190062 · Cited by 811
The blood-brain barrier in Alzheimer’s disease
Zenaro, E., Piacentino, G., & Constantin, G. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.07.007 · Cited by 767
Metadata
- Authors
- Storck, S. E., Meister, S., Nahrath, J., Meißner, J. N., Schubert, N., Di Spiezio, A., Baches, S., Vandenbroucke, R. E., Bouter, Y., Prikulis, I., Korth, C., Weggen, S., Heimann, A., Schwaninger, M., Bayer, T. A., & Pietrzik, C. U.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Universitätsmedizin Göttingen (DE)
- Heinrich Heine University Düsseldorf (DE)
- Ghent University (BE)
- University of Lübeck (DE)
- Corresponding author
- Meister, Sabrina
- Nahrath, Julius
- Pietrzik, Claus U.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2015-11-30
- Volume
- 126
- Issue
- 1
- Pages
- 123-136
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC4701557
- OpenAlex
- W2187829723
- Semantic Scholar
- 65f93af973d9bc910c701c3e4dfcbcb89ec826fe
- Cited by
- 477
- References
- 66
- Citations by year
- 2026: 61 · 2025: 58 · 2024: 55 · 2023: 59 · 2022: 40 · 2021: 53 · 2020: 43 · 2019: 30 · 2018: 24 · 2017: 33 · 2016: 20
- FWCI
- 13.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- GRO (submittedVersion, cc-by)
- Padua Research Archive (University of Padova) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (PI 379/8‐1)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- LRP1, amyloid-beta 42, blood-brain barrier, brain endothelium, Alzheimer's disease, amyloid-beta clearance, 5xFAD mice, spatial learning and memory deficits
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Cognition Disorders, Mice, Inbred C57BL, Peptide Fragments, Receptors, LDL, Amyloid beta-Peptides, Protein Transport, Tumor Suppressor Proteins, Low Density Lipoprotein Receptor-Related Protein-1, Endothelial Cells, Mice, Transcytosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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