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Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
Open accessAbstract
APOE genotype is a major genetic risk factor for late-onset Alzheimer disease (AD). ABCA1, a member of the ATP-binding cassette family of active transporters, lipidates apoE in the CNS. Abca1(-/-) mice have decreased lipid associated with apoE and increased amyloid deposition in several AD mouse models. We hypothesized that mice overexpressing ABCA1 in the brain would have increased lipidation of apoE-containing lipoproteins and decreased amyloid deposition. To address these hypotheses, we created PrP-mAbca1 Tg mice that overexpress mouse Abca1 throughout the brain under the control of the mouse prion promoter. We bred the PrP-mAbca1 mice to the PDAPP AD mouse model, a transgenic line overexpressing a mutant human amyloid precursor protein. PDAPP/Abca1 Tg mice developed a phenotype remarkably similar to that seen in PDAPP/Apoe(-/-) mice: there was significantly less amyloid beta-peptide (Abeta) deposition, a redistribution of Abeta to the hilus of the dentate gyrus in the hippocampus, and an almost complete absence of thioflavine S-positive amyloid plaques. Analyses of CSF from PrP-mAbca1 Tg mice and media conditioned by PrP-mAbca1 Tg primary astrocytes demonstrated increased lipidation of apoE-containing particles. These data support the conclusions that increased ABCA1-mediated lipidation of apoE in the CNS can reduce amyloid burden and that increasing ABCA1 function may have a therapeutic effect on AD.
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TL;DR
Overexpression of ABCA1 in the brain increased lipidation of apoE-containing lipoproteins and markedly reduced fibrillar amyloid deposition in PDAPP mice. The phenotype resembled PDAPP/Apoe−/− mice, supporting ABCA1/apoE lipidation as a potential AD therapeutic target.
Key findings
- PrP-mAbca1 transgenic mice overexpressed ABCA1 throughout the brain at approximately 2- to 14-fold across five lines; when crossed to PDAPP mice, PDAPP/Abca1 Tg mice had significantly less Aβ deposition, redistribution of Aβ to the hilus of the dentate gyrus, and almost no thioflavine S–positive amyloid plaques, similar to PDAPP/Apoe−/− mice.
- At 12 months, Aβ levels were approximately 2.5-fold lower in PDAPP/Abca1 line D and approximately 3-fold lower in line E versus non-Tg littermates; thioflavine S–positive amyloid was decreased by approximately 50% with 2-fold ABCA1 overexpression and to almost 0 with 6-fold or greater overexpression.
- At 3 months, before histological Aβ deposition, PDAPP/Abca1 line D and E Tg mice had 15%–50% higher Aβ levels than non-Tg controls, with no differences in APP or APP C-terminal fragments, suggesting altered clearance/transport rather than increased production.
- ABCA1 overexpression increased apoE lipidation: CSF apoE particles tended to be larger, astrocyte-conditioned media had a greater proportion of apoE particles larger than 11 nm, and lipoprotein fractions showed a significantly greater cholesterol-to-apoE ratio. High-expressing lines also had lower apoE in hippocampus (approximately 40%) and CSF (approximately 40%–70%), but line D reduced Aβ without lowering apoE.
Methods
- Mouse Abca1 cDNA was cloned into the MoPrP.HD-N171 vector to create PrP-mAbca1 Tg mice; five lines (D, E, L, J, G) with 2- to 14-fold brain ABCA1 overexpression were characterized, and lines D, E, and J were bred to the PDAPP AD mouse model.
- Mice were analyzed at 3 or 12 months with non-Tg littermate controls; outcomes included Aβ and thioflavine S histology/stereology, Aβ and apoE ELISAs, Western blotting, real-time RT-PCR, CSF and astrocyte-conditioned media lipoprotein analyses by nondenaturing gradient gel electrophoresis and size-exclusion chromatography, and testis histology/TUNEL/immunohistochemistry.
- Statistical comparisons used two-tailed Student’s t test or Mann-Whitney U test, with P < 0.05 considered significant.
Limitations
- The paper states that it is unclear whether increasing ABCA1 in adulthood may compromise male fertility, or whether ABCA1 can be selectively targeted to brain versus testes or other organs; male mice overexpressing ABCA1 at 6-fold or greater were infertile, with approximately 50% reduced testes mass and approximately 3-fold more apoptotic testicular cells.
- The paper notes that mechanisms linking increased apoE lipidation to altered Aβ transport, clearance, or aggregation were not directly tested, and that behavioral studies in APP Tg mice can be difficult to interpret.
- Evident from the text: findings are from transgenic mouse models with supraphysiological ABCA1 overexpression, some high-expressing lines had peripheral cholesterol changes of unknown mechanism, and several supporting observations are reported as data not shown.
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In the paper
“ranging from approximately 2-fold in line D to approximately 14-fold in line G (Figure 1A).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > The 5 lines of PrP-mAbca1
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In the paper
“Analysis of tissue from the occipital cortex, frontal cortex, hippocampus, cerebellum, striatum, septum, and thalamus showed that PrP-mAbca1 Tg mice overexpressed ABCA1 throughout the brain (Figure 1B).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > The 5 lines of PrP-mAbca1
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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 CSF, apoE levels were decreased by approximately 40%-70% in all lines overexpressing ABCA1 (Figure 6C).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > ApoE levels and solubility in PrP-mAbca1 Tg mice.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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 no difference between Tg and non-Tg apoE mRNA levels in either the hippocampus or cortex of either line (Figure 6D and data not shown).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > ApoE levels and solubility in PrP-mAbca1 Tg mice.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“overexpression of ABCA1 by 6-fold or greater resulted in reductions in hippocampal apoE of approximately 40% compared with non-Tg littermate control mice (Figure 6A).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > ApoE levels and solubility in PrP-mAbca1 Tg mice.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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 the APP and CTF bands using image analysis software revealed no significant differences between PDAPP/Abca1 Tg and PDAPP/ Abca1 non-Tg mice.”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Statistics.
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In the paper
“Compared with astrocytes derived from non-Tg mice, astrocytes derived from Tg mice secreted less apoE and associated cholesterol in HDL-like lipoproteins (Figure 7, C and D).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > ApoE levels and solubility in PrP-mAbca1 Tg mice.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Spermatogenesis defects in 3-month-old PrP-mAbca1 line E Tg mice.”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Statistics.
Strength:plain· not yet calibratedn = 5Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe 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
“In addition to the positive effects of overexpression of ABCA1 on Aβ, we did observe that male mice overexpressing ABCA1 at levels 6-fold or greater than those in normal brain were infertile.”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Discussion
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In the paper
“No elongated spermatids were present in testes from Tg mice.”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Statistics.
Strength:plain· not yet calibratedn = 5Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- It may state two separate claims as one. 16
- Probably not a substantial claim. 4
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 PDAPP mice with wild-type ABCA1 levels (PDAPP/Abca1 non-Tg mice) had frequent punctate Aβ deposits in the cortex and hippocampus (Figure 3A, top left panel), including the molecular layer of the hippocampus, but almost no Aβ deposits in the hilus of the dentate gyrus of the hippocampus (Figure 3A, middle left panel).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Amyloid deposition in the brains of PDAPP/Abca1 Tg mice.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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 contrast, the PDAPP mice with ABCA1 overexpression (PDAPP/Abca1 Tg mice) had rare Aβ deposition in the cortex (Figure 3A, top middle panel), occasional Aβ deposition in the molecular layer, and frequent Aβ deposition in the hilus of the dentate gyrus (Figure 3A, middle panel).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Amyloid deposition in the brains of PDAPP/Abca1 Tg mice.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Since decreases or increases in ABCA1 expression alter the absolute level of apoE without affecting Apoe transcription, understanding how ABCA1 alters apoE metabolism in the brain will be important.”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Discussion
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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, almost no thioflavine S-positive amyloid plaques were seen in the PDAPP/Abca1 Tg mice (Figure 3A, bottom middle panel) or in PDAPP/Apoe -/-mice (Figure 3A, bottom right panel), even in sections with extensive Aβ deposits.”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Amyloid deposition in the brains of PDAPP/Abca1 Tg mice.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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 the cortex, apoE was decreased by only approximately 20% in Tg mice from PrP-mAbca1 lines L, J, and G and was not decreased significantly in lines D or E (Figure 6B).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > ApoE levels and solubility in PrP-mAbca1 Tg mice.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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 Aβ load in the entire hippocampus did not vary significantly according to the presence of the mABCA1 transgene, but the distribution of Aβ within the hippocampus was altered by the transgene.”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Amyloid deposition in the brains of PDAPP/Abca1 Tg mice.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“PDAPP/Abca1 Tg mice had more Aβ deposition in the hilus of the dentate gyrus and less in the molecular layer (Figure 4A).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Amyloid deposition in the brains of PDAPP/Abca1 Tg mice.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“We found that PDAPP/Abca1 Tg mice had (a) decreased deposition of Aβ; (b) a near absence of thioflavine S-positive amyloid plaques; and (c) a redistribution of Aβ deposits in the hippocampus from the molecular layer to the hilus of the dentate gyrus.”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“APP Tg mice that are crossed to mice lacking Apoe develop significantly less Aβ deposition, and strikingly, the Aβ plaques that do form are almost all nonfibrillar and are not associated with neuritic dystrophy (20,23,24).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Introduction
What the sources say
- Not matchedcites [20]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [23]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [24]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“3 laboratories independently found that deletion of Abca1 either has no effect on or even increases Aβ deposition in 4 different mouse models of AD (20,23,24).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Introduction
What the sources say
- Not matchedcites [20]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [23]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [24]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
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In the paper
“demonstrating that lipid-poor apoE binds to fibrillar Aβ in vivo and likely promotes amyloidogenesis.”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Introduction
What the sources say
- Not matchedcites [23]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [24]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
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In the paper
“To control for genetic background effects, non-Tg littermate mice were always used as controls in experiments with the PrP-mAbca1 Tg mice from the appropriate line.”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Animals and tissue collection.
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In the paper
“The size of the decrease did not vary between lines that overexpressed ABCA1 6-fold to 14-fold, indicating that the effect is saturable.”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > ApoE levels and solubility in PrP-mAbca1 Tg mice.
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In the paper
“Activation of the transcription factor LXR has been shown to increase transcription of ABCA1 and many other genes involved in lipid metabolism and other pathways (50)(51)(52).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Discussion
What the sources say
- Not matchedcites (50)(51)(52)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“This phenotype strongly argues that overexpression of ABCA1 in the brain decreases the amyloidogenic properties of apoE and, further, that increased apoE lipidation results in a phenotype very similar to apoE deficiency with respect to Aβ metabolism.”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The PDAPP mouse model of AD recapitulates key features of human AD such that findings in this model are relevant to AD.
- Rests on an assumption: Aβ deposition and fibrillogenesis in mouse models are appropriate measures of AD pathology.
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
“Because this difference in apoJ levels was not observed in ABCA1 line D mice (data not shown), a 2-fold overexpression of ABCA1 in the brain is insufficient to significantly alter either apoJ or apoE levels (Figure 6A).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Effects of brain overexpression of ABCA1 on other proteins.
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In the paper
“In addition, lipidated apoE binds with a much higher affinity than poorly lipidated apoE to soluble Aβ (60).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Discussion
What the sources say
- Not matchedcites [60]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Previous in vitro work has shown that lipidated apoE forms an SDS-stable complex with Aβ to a greater extent than nonlipidated apoE (58,59).”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Discussion
What the sources say
- Not matchedcites [58]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [59]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- 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
“These higher levels do not represent deposited Aβ, as the mice did not have histological evidence of Aβ deposition at this age.”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Amyloid deposition in the brains of PDAPP/Abca1 Tg mice.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“There were no differences between PDAPP/Abca1 line E Tg and PDAPP/non-Tg mice (Figure 5E), suggesting that Aβ production was not likely to account for the differences in Aβ levels at 3 months.”
§ Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease > Amyloid deposition in the brains of PDAPP/Abca1 Tg mice.
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
The PDAPP mouse model of AD recapitulates key features of human AD such that findings in this model are relevant to AD.
“PDAPP AD mouse model, a transgenic line overexpressing a mutant human amyloid precursor protein.”
“increasing ABCA1 function may have a therapeutic effect on AD.”
The paper relies on this without support.
Aβ deposition and fibrillogenesis in mouse models are appropriate measures of AD pathology.
“These data support the conclusions that increased ABCA1-mediated lipidation of apoE in the CNS can reduce amyloid burden and that increasing ABCA1 function may have a therapeutic effect on AD.”
The paper relies on this without support.
The effects of ABCA1 overexpression on Aβ deposition are not due to altered expression of other proteins outside those tested.
“No differences were found in the levels of low-density lipoprotein receptor (LDLR), LDLR-related protein 1 (LRP1), and apoA-I when comparing ABCA1 line E Tg mice to non-Tg littermates (Figure 8, A and B).”
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
“Conversely, increasing Abca1 expression, and subsequently apoE lipidation, reduces Aβ peptides and plaque deposition. 13”
From Deletion of miR-33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice (2024) · cites this paper as [13]
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
“ABCA1 overexpression or LXR/RXR agonist treatment decreased amyloid deposition [66-69].”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [69]
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
“Both the overexpression and deletion of ABCA1 in the mouse brain resulted in a decrease in apoE protein level [28-30].”
From Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling (2012) · cites this paper as [30]
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
“However, the apoE containing lipoprotein particles isolated from the cerebral spinal fluid (CSF) of ABCA1−/− mice were poorly lipidated, while those from the CSF of mice overexpressing ABCA1 had higher levels of lipidation compared to Wt animals [28,30].”
From Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling (2012) · cites this paper as [30]
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
“In addition, several studies have demonstrated that increasing apoE lipidation, either through genetic or pharmacological approaches, promotes Aβ clearance and improves cognitive performance in mice (27, 44, 45).”
From APOE3 -Jacksonville (V236E) variant reduces self-aggregation and risk of dementia (2021) · cites this paper as [44]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“because the extent of apoE lipidation may also play a role in modulating Aβ accumulation (41)”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [41]
The cited source says what the claim attributes to it.
In the citing paper
“This finding is consistent with a previous report that demonstrated no change in apoE protein levels when ABCA1 was overexpressed 2‐ or 6‐fold over the endogenous level in the cortex. 13”
From Deletion of miR-33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice (2024) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“ABCA1 gene ablation in mice decreased APOE lipidation and levels and increased Aβ accumulation in APP transgenic mouse models.”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [69]
The cited source says what the claim attributes to it.
In the citing paper
“whereas ABCA1 overexpression ameliorated Aβ accumulation (Donkin et al., 2010; Wahrle et al., 2008).”
From miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression (2012) · cites this paper as Wahrle et al., 2008
The cited source says what the claim attributes to it.
In the citing paper
“In the brain, the level of ABCA1 has been shown to modulate the extent of apoE lipidation and apoE levels.”
From Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling (2012) · cites this paper as [30]
The cited source says what the claim attributes to it.
In the citing paper
“Brain levels of the cholesterol transporter ATP binding cassette A1 (ABCA1) also alter the amount of apoE and the extent of apoE lipidation in mice.”
From Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling (2012) · cites this paper as [30]
The cited source says what the claim attributes to it.
In the citing paper
“In transgenic mice that overexpress the human amyloid precursor protein (APP), increasing ABCA1 levels caused a significant decrease in amyloid deposition in the brain [30].”
From Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling (2012) · cites this paper as [30]
The cited source says what the claim attributes to it.
In the citing paper
“ATP-binding cassette transporter A1 (ABCA1) overexpression in APP transgenic mice also showed a similar phenotype (Wahrle et al., 2008).”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as Wahrle et al., 2008
The cited source says what the claim attributes to it.
In the citing paper
“When these mice, which had greater apoE lipidation, were crossed with PDAPP mice, there was a dramatic decrease in the amount of Aβ deposition and thioflavine-S positive plaques in the ABCA1 transgenic mice (Wahrle et al., 2008).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Wahrle et al., 2008
The cited source says what the claim attributes to it.
In the citing paper
“Over a decade of evidence demonstrates that the cell-surface lipid transporter ATP binding cassette subfamily A member 1 (ABCA1) modulates AD pathogenesis, with ABCA1 antagonism increasing, and agonism decreasing, pathology [48–51].”
From Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation (2023) · cites this paper as [49]
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, overexpressing ABCA1 increases the percentage of lipidated ApoE fractions and reduces A accumulation (Wahrle et al., 2008).”
From ApoE4 Alters ABCA1 Membrane Trafficking in Astrocytes (2019) · cites this paper as Wahrle et al., 2008
The cited source says what the claim attributes to it.
In the citing paper
“This transporter is of prime interest in AD because its impact on brain cholesterol metabolism modulates the brain's amyloid burden.”
The cited source says what the claim attributes to it.
In the citing paper
“In a mouse model, improved ApoE lipidation by the overexpression of ATP-binding cassette transporter family member A1 (ABCA1) decreased plaque deposition (Wahrle et al., 2005; Wahrle et al., 2008; Wahrle et al., 2004).”
From NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load (2021) · cites this paper as Wahrle et al., 2008
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Previous research has shown that the overexpression of ABCA1 ameliorated Aβ pathology in a mouse model of Aβ amyloidosis and that treatment with an LXR agonist was protective in a mouse model of tau-mediated neurodegeneration (65, 66).”
From Lipidome and proteome of astrocyte and microglia ApoE lipoprotein reveal differences based on cell type and ApoE isoform (2026) · cites this paper as [66]
Experimental — accuracy not yet measuredIn the citing paper
“In contrast, overexpression of ABCA1 led to a decrease in Aβ plaques (Fig. 2B) [43].”
From ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer’s disease and related disorders (2026) · cites this paper as [43]
In the citing paper
“Whereas overexpression of ABCA1 decreases the amyloid accumulation [14]”
In the citing paper
“whereas overexpression of the gene decreases amyloid deposition and improves the animals' behavior [14].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Three-month cortical Aβ40 total does not equal its components
MinorFor the line D transgenic group, carbonate Aβ40 of 0.23 plus guanidine Aβ40 of 0.05 gives 0.28, not the reported total of 0.73.
Reported 0.73 · recomputed 0.28
“| +, n = 11 | 0.23 ± 0.09 | 0.35 ± 0.08 | 0.05 ± 0.07 | 0.86 ± 0.13 | 0.73 ± 0.12 | 1.21 ± 0.11 |”
Citations
Cites
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268
Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., et al. (1999) · Science · doi:10.1126/science.286.5440.735 · Cited by 3,876
Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein
Games, D., Adams, D., Alessandrini, R., Barbour, R., Borthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F., et al. (1995) · Nature · doi:10.1038/373523a0 · Cited by 2,516
The plasma lecithin:cholesterol acyltransferase reaction
Glomset, J. A. (1968) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)43114-1 · Cited by 2,396
Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency
Brooks-Wilson, A., Marcil, M., Clee, S. M., Zhang, L.-H., Roomp, K., van Dam, M., Yu, L., Brewer, C., Collins, J. A., Molhuizen, H. O. F., et al. (1999) · Nature Genetics · doi:10.1038/11905 · Cited by 1,687
Schmechel, D. E., Saunders, A. M., Strittmatter, W. J., Crain, B. J., Hulette, C. M., Joo, S. H., Pericak-Vance, M. A., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.20.9649 · Cited by 1,525
The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease
Bodzioch, M., Orsó, E., Klucken, J., Langmann, T., Böttcher, A., Diederich, W., Drobnik, W., Barlage, S., Büchler, C., Porsch-Özcürümez, M., et al. (1999) · Nature Genetics · doi:10.1038/11914 · Cited by 1,512
Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1
Rust, S., Rosier, M., Funke, H., Real, J., Amoura, Z., Piette, J.-C., Deleuze, J.-F., Brewer, H. B., Duverger, N., Denèfle, P., et al. (1999) · Nature Genetics · doi:10.1038/11921 · Cited by 1,433
Strittmatter, W. J., Weisgraber, K. H., Huang, D. Y., Dong, L. M., Salvesen, G. S., Pericak-Vance, M., Schmechel, D., Saunders, A. M., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.8098 · Cited by 1,363
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Items 101–200 of 372
Skerrett, R., Pellegrino, M. P., Casali, B. T., Taraboanta, L., & Landreth, G. E. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.652008 · Cited by 91
“The ability of apoE to facilitate soluble Aβ clearance is strongly dependent on the apoE isoform (3,4,5) and its lipidation state, with ABCA1-dependent lipidation playing an important role (11,12,13).”
BackgroundLipoproteins in the Central Nervous System: From Biology to Pathobiology
Raulin, A.-C., Martens, Y. A., & Bu, G. (2022) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-032620-104801 · Cited by 89
MicroRNA Regulation of Cholesterol Metabolism
Rotllán, N., & Fernandez-Hernando, C. F. (2012) · Cholesterol · doi:10.1155/2012/847849 · Cited by 87
“Genetic studies with Alzheimer disease (AD) mouse models have demonstrated that the deletion of ABCA1 increases Aβ deposition, while overexpression of ABCA1 dramatically reduces Aβ deposition, suggesting a role for ABCA1 in Aβ metabolism [22, 74–76].”
BackgroundGenomic convergence and network analysis approach to identify candidate genes in Alzheimer's disease
Talwar, P., Silla, Y., Grover, S., Gupta, M., Agarwal, R., Kushwaha, S. S., & Kukreti, R. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-199 · Cited by 86
“A recently found strong LOAD candidate is PTK2B/ CAKB/FAK2/PYK2 gene that encodes for a cytoplasmic protein tyrosine kinase, which is highly expressed in the CNS, particularly in HIP [73].”
BackgroundRasmussen, K. L., Tybjærg-Hansen, A., Nordestgaard, B. G., & Frikke-Schmidt, R. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz402 · Cited by 86
The benefit of docosahexaenoic acid for the adult brain in aging and dementia
Salem, N., Vandal, M., & Calon, F. (2014) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2014.10.003 · Cited by 86
Role of ABCA7 in Human Health and in Alzheimer’s Disease
Dib, S., Pahnke, J., & Gosselet, F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094603 · Cited by 88
McGrowder, D. A., Riley, C. K., Morrison, E., & Gordon, L. (2010) · Cholesterol · doi:10.1155/2011/496925 · Cited by 85
“Further, brain HDL can suppress Aβ production by decreasing cellular cholesterol through the activation of reverse cholesterol transport mediated by ABC transporters [81].”
BackgroundFernández-de Frutos, M., Galán-Chilet, I., Goedeke, L., Kim, B., Pardo-Marqués, V., Pérez-García, A., Herrero, J. I., Fernández-Hernando, C., Kim, J., & Ramírez, C. M. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00170-19 · Cited by 82
“ABCA1, one of the most studied transcriptional targets of LXR, affects the lipidation status of ApoE in the brain, which in turn may facilitate the proteolytic degradation of A (30).”
BackgroundSelf-citationLXR Agonists: New Potential Therapeutic Drug for Neurodegenerative Diseases
Xu, P., Li, D., Tang, X., Bao, X., Huang, J., Tang, Y., Yang, Y., Xu, H., & Fan, X. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8461-3 · Cited by 84
“In contrast, overexpression of ABCA1 reduces amyloid deposition in the human APP V717F mouse model of AD [86, 87].”
BackgroundApolipoprotein E in Alzheimer’s disease: molecular insights and therapeutic opportunities
Belaidi, A. A., Bush, A. I., & Ayton, S. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00843-y · Cited by 91
“Conversely, increasing apoE lipidation via ABCA1 over-expression in AD mice reduced Aβ plaque load with the opposing effect in ABCA1-deficient mice [169, 170].”
Apolipoprotein E: Essential Catalyst of the Alzheimer Amyloid Cascade
Potter, H., & Wısnıewskı, T. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/489428 · Cited by 84
“Together these results show that inflammatory proteins, particularly apoE, are integral parts of the amyloid cascade, and that without them the cascade would be arrested at the level of the harmless Aβ monomer, and no AD would ensue.”
BackgroundBatarseh, Y. S., & Kaddoumi, A. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.12.006 · Cited by 83
“suggested that ABCA1 overproduction reduced Aβ deposition both in the soluble and insoluble forms in vivo [34].”
BackgroundABC transporters: human disease and pharmacotherapeutic potential
Moore, J. M., Bell, E. L., Hughes, R. O., & Garfield, A. S. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2022.11.001 · Cited by 94
Baldán, Á., Bojanic, D. D., & Edwards, P. A. (2008) · Journal of Lipid Research · doi:10.1194/jlr.r800044-jlr200 · Cited by 81
Amyloid-β42 alters apolipoprotein E solubility in brains of mice with five familial AD mutations
Youmans, K. L., Leung, S., Zhang, J., Maus, E., Baysac, K., Bu, G., Vassar, R., Yu, C., & LaDu, M. J. (2011) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2010.12.025 · Cited by 62
“N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript 1991; Wahrle et al., 2008; Weidemann et al., 1989).”
BackgroundCholesterol-related genes in Alzheimer's disease
Wollmer, M. A. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.05.009 · Cited by 78
Halford, R. W., & Russell, D. W. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813349106 · Cited by 75
Behl, T., Kaur, I., Sehgal, A., Kumar, A., Uddin, M. S., & BUNGAU, S. G. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02211-x · Cited by 78
Apolipoprotein E Genotype Affects Size of ApoE Complexes in Cerebrospinal Fluid
Heinsinger, N. M., Gachechiladze, M. A., & Rebeck, G. W. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlw067 · Cited by 74
“Overexpression of ABCA1 may increase Ab clearance in the brain (39) because increased lipidation of apoE facilitates proteolytic degradation of Ab (40).”
BackgroundHubin, E., Verghese, P. B., van Nuland, N., & Broersen, K. (2019) · FEBS Letters · doi:10.1002/1873-3468.13428 · Cited by 73
Remembering your A, B, C's: Alzheimer's disease and ABCA1
Lewandowski, C. T., Laham, M. S., & Thatcher, G. R. J. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.01.011 · Cited by 76
Apelin, a promising target for Alzheimer disease prevention and treatment
Masoumi, J., Abbasloui, M., Parvan, R., Mohammadnejad, D., Pavon‐Djavid, G., Barzegari, A., & Abdolalizadeh, J. (2018) · Neuropeptides · doi:10.1016/j.npep.2018.05.008 · Cited by 70
Lewandowski, C. T., Maldonado Weng, J., & LaDu, M. J. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104811 · Cited by 72
Zandl‐Lang, M., Fanaee‐Danesh, E., Sun, Y., Albrecher, N. M., Gali, C. C., Čančar, I., Kober, A. C., Tam‐Amersdorfer, C., Stracke, A., Storck, S. E., et al. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2017.09.008 · Cited by 73
Malar, D. S., Suryanarayanan, V., Prasanth, M. I., et al. (2018) · Toxicology in Vitro · doi:10.1016/j.tiv.2018.03.003 · Cited by 68
Saint-Pol, J., Vandenhaute, E., Boucau, M.-C., Candela, P., Dehouck, L., Cecchelli, R., Dehouck, M.-P., Fenart, L., & Gosselet, F. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-112090 · Cited by 64
“Furthermore, Abca1-overexpressing AD mice show a decrease in amyloid burden [55], whereas Abca1 deficiency promotes deposition [56–58].”
Adorni, M. P., Ruscica, M., Ferri, N., Bernini, F., & Zimetti, F. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00120 · Cited by 67
Corona, A. W., Kodoma, N., Casali, B. T., & Landreth, G. E. (2015) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9627-8 · Cited by 69
“It is likely that ABCA1 deficiency is at least a partial cause of the increased Aβ pathology in ABCA1 KO mice, because genetic overexpression of ABCA1 caused an opposing effect, with a pronounced reduction in levels of soluble Aβ and plaques (Wahrle et al. 2008).”
Lei, C., Lin, R., Wang, J., Tao, L., Fu, X., Qiu, Y., & Lei, B. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.07.053 · Cited by 66
Burgess, B. L., Parkinson, P. F., Racke, M. M., Hirsch‐Reinshagen, V., Fan, J., Wong, C. A., Stukas, S. K., Théroux, L., Chan, J. Y., Donkin, J. J., et al. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m700481-jlr200 · Cited by 66
Self-citationMemory Deficits in APP23/ Abca1 +/− Mice Correlate with the Level of A β Oligomers
Lefterov, I. M., Fitz, N. F., Cronican, A. A., Lefterov, P., Staufenbiel, M., & Koldamova, R. P. (2009) · ASN NEURO · doi:10.1042/an20090015 · Cited by 63
“In addition, recent data suggest that properly lipidated brain ApoE and ApoA-I lipoproteins are necessary for Ab degradation and clearance of amyloid deposits (Jiang et al., 2008; Wahrle et al., 2008).”
BackgroundThe small HDL particle hypothesis of Alzheimer's disease
Martinez, A. E., Weissberger, G. H., Kuklenyik, Z., He, X., Meuret, C. J., Parekh, T., Rees, J. C., Parks, B. A., Gardner, M. S., King, S. M., et al. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12649 · Cited by 63
Co-aggregation with Apolipoprotein E modulates the function of Amyloid-β in Alzheimer’s disease
Xia, Z., Prescott, E. E., Urbanek, A., Wareing, H. E., King, M. C., Olerinyova, A., Dakin, H., Leah, T., Barnes, K. A., Matuszyk, M. M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49028-z · Cited by 67
“…deleting the ATP-binding cassette transporter 1 (ABCA1) - which regulates apoE lipidation in the CNS 17 – increases the deposition of A β plaques 70,71 , while overexpressing or upregulating ABCA1 relieves cognitive impairment caused by A β and reverses memory de fi cits intransgenic animals 72 .”
BackgroundSelf-citationLuo, Y., Yang, L.-L., & Yao, X. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00720-0 · Cited by 75
“The deficiency of ABCA1 results in impaired APOE lipidation, leading to increased Aβ plaque load, while overexpression of ABCA1 can reduce Aβ deposition [167, 168].”
BackgroundHe, S., Xu, Z., & Han, X. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00803-6 · Cited by 62
“In vivo studies concluded that ABCA1 deficiency increases, while its overexpression reduces Aβ deposition [347, 348].”
Effects of oxysterols on the blood–brain barrier: Implications for Alzheimer’s disease
Gosselet, F., Saint-Pol, J., & Fenart, L. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.11.059 · Cited by 53
“It is, however, likely that the effect of oxysterols on BBB cholesterol homeostasis modifies the lipoprotein content of the brain and consequently, indirectly Ab peptide clearance [59,60].”
BackgroundMinh, T. N., Dodacki, A., Alata, W., Calon, F., Nicolic, S., Scherrmann, J., Farinotti, R., & Bourasset, F. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150350 · Cited by 65
“There have been several reports of a reciprocal relationship between the amount of Abca1 in the brain and the cerebral A level [35, 54, 55].”
BackgroundCzuba, E., Steliga, A., Lietzau, G., & Kowiański, P. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-0015-3 · Cited by 62
“It has been previously reported that APOE level is reduced in abca1gene-knockout mice (Wahrle et al. 2008).”
BackgroundLoane, D. J., Washington, P. M., Vardanian, L., Pocivavsek, A., Hoe, H.-S., Duff, K. E., Cernak, I., Rebeck, G. W., Faden, A. I., & Burns, M. P. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2010.1595 · Cited by 57
“Conversely, overexpression of ABCA1 in APP-transgenic mice reduces Ab deposition (Wahrle et al., 2008).”
BackgroundHeart fatty acid binding protein and Aβ-associated Alzheimer’s neurodegeneration
Desikan, R. S., Thompson, W. K., Holland, D., Hess, C. P., Brewer, J. B., Zetterberg, H., Blennow, K., Andreassen, O. A., McEvoy, L. K., Hyman, B. T., et al. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-39 · Cited by 59
“However, in animal models, apolipoprotein E modulates the relationship between low-density lipoproteins and amyloid-β (Aβ) deposition [6,7] suggesting an indirect effect of intra-cranial cholesterol on Alzheimer’s pathology.”
BackgroundHuttunen, H. J., Havas, D., Peach, C., Barren, C., Duller, S., Xia, W., Frosch, M. P., Hutter-Paier, B., Windisch, M., & Kovacs, D. M. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181e77ed9 · Cited by 54
“Moreover, the level and lipidation status of brain ApoE strongly affects AA deposition (23, 26).”
The role of ATP-binding cassette subfamily A in the etiology of Alzheimer’s disease
Bossaerts, L., Cacace, R., & Broeckhoven, C. V. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00536-w · Cited by 56
“In parallel, overexpression of Abca1 in an AD mouse model reduced fibrillogenesis and deposition of Aβ in the brain, possibly related to the increased lipidation of ApoE [63].”
Background25-Hydroxycholesterol in health and diseases
Nguyen, C. M., Saint‐Pol, J., Dib, S., Pot, C., & Gosselet, F. (2023) · Journal of Lipid Research · doi:10.1016/j.jlr.2023.100486 · Cited by 59
“…mimicking the neurodegenerative disorder Alz-heimer ’ s disease (AD), stimulating LXR/ABCA1 axis with agonists (T0901317 or GW3965), or increasing Abca1 expression alleviates the disorder, while deleting Abca1 expression aggravates the β -amyloid burden which is characteristic of AD (44 – 46).”
BackgroundThe Role of ABCA1 Gene Sequence Variants on Risk of Alzheimer's Disease
Lupton, M. K., Proitsi, P., Lin, K., Hamilton, G., Daniilidou, M., Tsolaki, M., & Powell, J. F. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-131121 · Cited by 57
“These mechanisms have been dissected in animal studies by crossing transgenic mice that express mutant AβPP and form A containing plaques with mice with deleted or overexpression of ABCA1 [15, 16].”
Yang, J., Kou, J., Lalonde, R., & Fukuchi, K.-I. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.05.012 · Cited by 57
“The depletion and overexpression of ABCA1 increases and decreases brain Aβ in AD mouse models, respectively (Wahrle et al., 2005; Wahrle et al., 2008).”
BackgroundFu, Y., Hsiao, J.-H. T., Paxinos, G., Halliday, G. M., & Kim, W. S. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-141320 · Cited by 58
“In the case of ABCA1, it was suggested that ABCA1 serves a protective role that is related to apoE lipidation and A clearance [23, 32].”
Kuntz, M., Candela, P., Saint-Pol, J., Lamartinière, Y., Boucau, M.-C., Sevin, E., Fenart, L., & Gosselet, F. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-150469 · Cited by 55
“deletion of ABCA1 expression increases the amyloid burden in murine models of AD [11–13], whereas overexpression of the gene decreases amyloid deposition and improves the animals’ behavior [14].”
Emerging role of HDL in brain cholesterol metabolism and neurodegenerative disorders
Turri, M., Marchi, C., Adorni, M. P., Calabresi, L., & Zimetti, F. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2022.159123 · Cited by 54
Wu, M., Zhai, Y., Liang, X., Chen, W., Lin, R., Ma, L., Huang, Y., Zhao, D., Liang, Y., Zhao, W., et al. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.842814 · Cited by 59
“Gene overexpression of ABCA1 can reduce Aβ and plaque (Wahrle et al., 2008).”
BackgroundOverview of the blood biomarkers in Alzheimer's disease: Promises and challenges
Delaby, C., Hirtz, C., & Lehmann, S. (2022) · Revue Neurologique · doi:10.1016/j.neurol.2022.09.003 · Cited by 60
A-Subclass ATP-Binding Cassette Proteins in Brain Lipid Homeostasis and Neurodegeneration
Piehler, A. P., Özcürümez, M. K., & Kaminski, W. E. (2012) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2012.00017 · Cited by 61
“According to their predicted primary structure, ABCA transporters www.frontiersin.org March 2012 | Volume 3 | Article 17 | 1 FIGURE 1 | Schematic view of an A-subclass ABC transporter.”
BackgroundInfluentialInteractions of metals and Apolipoprotein E in Alzheimer’s disease
Xu, H. J., Finkelstein, D. I., & Adlard, P. A. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00121 · Cited by 56
“Some ApoE receptors and ABCA1 appear to influence ApoE expression and lipidation (Hirsch-Reinshagen et al., 2004; Wahrle et al., 2004; Fryer et al., 2005a; Liu et al., 2007; Wahrle et al., 2008).”
BackgroundMolecular Insight into the Therapeutic Promise of TargetingAPOE4for Alzheimer’s Disease
Mamun, A. A., Uddin, M. S., Bashar, M. F. B., Zaman, S., Begum, Y., Bulbul, I. J., Islam, M. S., Sarwar, M. S., Mathew, B., Amran, M. S., et al. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/5086250 · Cited by 54
“Conversely, ABCA1 overexpression diminishes the accumulation of Aβ in an APOEdependent way in the amyloid mouse model [117], which recommends a favorable role of ABCA1-induced APOE lipidation for the stopping of the AD pathogenesis (Figure 3).”
BackgroundBrain lipid metabolism, apolipoprotein E and the pathophysiology of Alzheimer's disease
Bales, K. R. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.01.005 · Cited by 58
“Conversely, when ABCA1 is overexpressed in APP transgenic mice, maximal lipidation of apoE occurs and brain Ab levels are reduced (Wahrle et al., 2008).”
Self-citationChernick, D., Ortiz‐Valle, S., Jeong, A., Swaminathan, S. K., Kandimalla, K. K., Rebeck, G. W., & Li, L. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14554 · Cited by 51
ABCA8 stimulates sphingomyelin production in oligodendrocytes
Kim, W. S., Hsiao, J.-H. T., Bhatia, S., Glaros, E. N., Don, A. S., Tsuruoka, S., Weickert, C. S., & Halliday, G. M. (2013) · Biochemical Journal · doi:10.1042/bj20121764 · Cited by 53
Namjoshi, D., Martin, G., Donkin, J. J., Wilkinson, A., Stukas, S. K., Fan, J., Carr, M., Tabarestani, S., Wuerth, K. C., Hancock, R. E. W., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053529 · Cited by 56
“Conversely, overexpression of ABCA1 in the CNS increases apoE lipidation and greatly decreases amyloid deposits in AD mice [38].”
BackgroundSelf-citationLiver X receptor modulators: a review of recently patented compounds (2007 – 2009)
Li, X., Yeh, V. S. C., & Molteni, V. (2010) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543771003621269 · Cited by 54
“As LXR agonists induce expression of cholesterol transporter protein ABCA1 and ApoE in the brain, it is suggested that LXR agonists could potentially be used to treat AD by increasing the clearance of Abeta [32,33].”
BackgroundSmall molecule inducers of ABCA1 and apoE that act through indirect activation of the LXR pathway
Fan, J., Zhao, R. Q., Parro, C., Zhao, W., Chou, H.-Y., Robert, J., Deeb, T. Z., Raynoschek, C., Barichievy, S., Engkvist, O., et al. (2018) · Journal of Lipid Research · doi:10.1194/jlr.m081851 · Cited by 50
“ABCA1 increases CNS apoE lipidation and markedly decreases amyloid deposition (6).”
BackgroundSelf-citationFanaee‐Danesh, E., Gali, C. C., Tadić, J., Zandl‐Lang, M., Kober, A. C., Agujetas, V. R., de Dios, C., Tam‐Amersdorfer, C., Stracke, A., Albrecher, N. M., et al. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.04.019 · Cited by 53
Choi, J., Gao, J., Kim, J., Hong, C., Kim, J., & Tontonoz, P. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aad1904 · Cited by 49
Self-citationBurris, T. P., de Vera, I. M. S., Côté, I., Flaveny, C. A., Wanninayake, U. S., Chatterjee, A., Walker, J. K., Steinauer, N., Zhang, J., Coons, L. A., et al. (2023) · Pharmacological Reviews · doi:10.1124/pharmrev.121.000436 · Cited by 54
microRNAs: A connection between cholesterol metabolism and neurodegeneration
Goedeke, L., & Fernandez-Hernando, C. F. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.034 · Cited by 49
“…studies using genetically modified mouse models of Alzheimer’s disease have shown that ABCA1 deficiency significantly reduces levels of APOE and increases Aβ and amyloid deposition, while overexpression of ABCA1 ameliorates Aβ accumulation (Fitz et al, 2012; Wahrle et al, 2005; Wahrle et al, 2008).”
BackgroundSaint-Pol, J., Candela, P., Boucau, M.-C., Fenart, L., & Gosselet, F. (2013) · Brain Research · doi:10.1016/j.brainres.2013.04.008 · Cited by 50
“Furthermore, overexpression of Abca1 decreases the amyloid burden (Wahrle et al., 2008), whereas Abca1 deletion promotes the AD phenotype (Fitz et al., 2012; HirschReinshagen et al., 2005; Koldamova et al., 2005a; Wahrle et al., 2005).”
BackgroundRole of Abca7 in Mouse Behaviours Relevant to Neurodegenerative Diseases
Logge, W., Cheng, D., Chesworth, R., Bhatia, S., Garner, B., Kim, W. S., & Karl, T. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045959 · Cited by 49
“Interestingly, validated mouse models for familial AD have shown disrupted spatial reference memory and object recognition [23–25] and deficiency in Abca1, which is one of the main ABC transporters and essential for cholesterol homeostasis, exacerbated amyloidogenesis in amyloid mouse models of AD [26,27], whereas Abc…”
BackgroundAdvances in high-density lipoprotein physiology: surprises, overturns, and promises
Constantinou, C., Karavia, E. A., Xepapadaki, E., Πετροπούλου, Π.-Ι., Παπακώστα, Ε., Karavyraki, M., Zvintzou, E., Theodoropoulos, V., Filou, S., Hatziri, A., et al. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00429.2015 · Cited by 48
Apolipoprotein D modulates amyloid pathology in APP/PS1 Alzheimer's disease mice
Li, H., Ruberu, K. R., Muñoz, S. S., Jenner, A. M., Spiro, A. S., Zhao, H., Rassart, É., Sánchez, D., Ganfornina, M. D., Karl, T., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.02.010 · Cited by 48
“For example, expression of the lipid transport protein ATP-binding cassette transporter A1 (ABCA1) is increased in the brain in human AD and AD mouse models (Kim et al., 2010), yet transgenic expression of ABCA1 in AD mice significantly reduces plaque pathology (Wahrle et al., 2008).”
ABCG1 and ABCG4 Suppress γ-Secretase Activity and Amyloid β Production
Sano, O., Tsujita, M., Shimizu, Y., Kato, R., Kobayashi, A., Kioka, N., Remaley, A. T., Michikawa, M., Ueda, K., & Matsuo, M. (2016) · PLOS ONE · doi:10.1371/journal.pone.0155400 · Cited by 47
Lamartinière, Y., Boucau, M.-C., Dehouck, L., Krohn, M., Pahnke, J., Candela, P., Gosselet, F., & Fenart, L. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-170883 · Cited by 50
“Regarding cholesterol homeostasis, elevated ABCA1 expression in the AD mouse was associated with less amyloid deposition and less aberrant behavior [53–55].”
Jia, Y., Wang, N., Zhang, Y., Xue, D., Lou, H., & Liu, X. (2020) · Aging and Disease · doi:10.14336/ad.2019.0519 · Cited by 50
“The author further found that overexpression of Abca1 in the mouse brain increases ApoE lipidation and decreases Aβ deposition [121].”
BackgroundAlzheimer's disease: brain expression of a metabolic disorder?
Merlo, S., Spampinato, S. F., Canonico, P. L., Copani, A., & Sortino, M. A. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.05.005 · Cited by 50
NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load
Pohlkamp, T., Xian, X., Wong, C. H., Durakoglugil, M. S., Werthmann, G. C., Saido, T. C., Evers, B. M., White, C. L., Connor, J., Hammer, R. E., et al. (2021) · eLife · doi:10.7554/elife.72034 · Cited by 46
Iron Regulates Apolipoprotein E Expression and Secretion in Neurons and Astrocytes
Xu, H. J., Perreau, V. M., Dent, K. A., Bush, A. I., Finkelstein, D. I., & Adlard, P. A. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150797 · Cited by 45
“Some ApoE receptors and the ATP binding cassette A1 (ABCA1) have been found to influence ApoE protein expression [49–53].”
Neuroprotective Effects of Lactoferrin in Alzheimer’s and Parkinson’s Diseases: A Narrative Review
Yong, S. J., Veerakumarasivam, A., Lim, W. L., & Chew, J. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.2c00679 · Cited by 46
MicroRNA regulation of cholesterol metabolism
Citrin, K. M., Fernandez-Hernando, C. F., & Suárez, Y. (2021) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14566 · Cited by 45
ApoE-isoform-dependent cellular uptake of amyloid-β is mediated by lipoprotein receptor LR11/SorLA
Yajima, R., Tokutake, T., Koyama, A., Kasuga, K., Tezuka, T., Nishizawa, M., & Ikeuchi, T. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.11.111 · Cited by 43
The pleiotropic vasoprotective functions of high density lipoproteins (HDL)
Boyce, G. K., Button, E. B., Sonja, S. V., & Wellington, C. L. (2017) · Journal of Biomedical Research · doi:10.7555/jbr.31.20160103 · Cited by 41
“[210] Wahrle SE, Jiang H, Parsadanian M, et al.”
BackgroundSelf-citationTargeting Apolipoprotein E for Alzheimer’s Disease: An Industry Perspective
Suidan, G. L., & Ramaswamy, G. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092161 · Cited by 42
“In contrast, abca1 overexpression in mice increases lipidation of apoE and enhances amyloid clearance [29].”
BackgroundRaman, S., Brookhouser, N., & Brafman, D. A. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104788 · Cited by 41
The impact of rare genetic variants on Alzheimer disease
Deyn, L. D., & Sleegers, K. (2025) · Nature Reviews Neurology · doi:10.1038/s41582-025-01062-1 · Cited by 46
“Similarly, overexpression of ABCA1 in PDAPP mice influences the lipid uptake by APOE and thus reduces Aβ deposition 96 .”
Activation of Liver X Receptor Protects Inner Retinal Damage Induced by N-methyl-D-aspartate
Zheng, S., Yang, H., Chen, Z., Zheng, C., Lei, C., & Lei, B. (2015) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-15612 · Cited by 41
Interrelationship between ATP-binding cassette transporters and oxysterols
Ruiz, J. L. M., Rosa-Fernandes, L., Levy, D., et al. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.02.033 · Cited by 41
“ABCA2 is mainly expressed in brain and nervous tissues, with particularly high expression in cells facilitating myelin production in the brain (oligodendrocytes) and peripheral nerves (Schwann cells) [50].”
BackgroundXiao, Z.-J., Wang, J., Chen, W., Wang, P., Zeng, H., & Chen, W. (2012) · Lipids in Health and Disease · doi:10.1186/1476-511x-11-163 · Cited by 43
“Several studies with AD mouse model revealed that ABCA1 expression could regulate the level of apoE lipidation and the production of Aβ [32-35].”
BackgroundMadadi, S., Schwarzenbach, H., Saidijam, M., Mahjub, R., & Soleimani, M. (2019) · Cell & Bioscience · doi:10.1186/s13578-019-0354-3 · Cited by 41
Association of ATP-Binding Cassette Transporter Variants With the Risk of Alzheimer‘s Disease
Cascorbi, I., Flüh, C., Remmler, C., Haenisch, S., Faltraco, F., Grumbt, M., Peters, M., Brenn, A., Thal, D. R., Warzok, R., et al. (2013) · Pharmacogenomics · doi:10.2217/pgs.13.18 · Cited by 41
Sex Hormone Decline and Amyloid β Synthesis, Transport and Clearance in the Brain
Duarte, A. C., Hrynchak, M. V., Gonçalves, I., Quintela, T., & Santos, C. R. A. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12432 · Cited by 42
Abdelhamid, M., Jung, C., Zhou, C., Abdullah, M., Nakano, M., Wakabayashi, H., Abe, F., & Michikawa, M. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191181 · Cited by 41
Li, G., Kim, C., Kim, J., Yoon, H., Zhou, H., & Kim, J. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-150024 · Cited by 39
Self-citationMulti-functional role of apolipoprotein E in neurodegenerative diseases
Islam, S., Noorani, A. A., Sun, Y., Michikawa, M., & Zou, K. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1535280 · Cited by 43
Metals and cholesterol: two sides of the same coin in Alzheimer’s disease pathology
Wong, B. X. W., Hung, Y. H., Bush, A. I., & Duce, J. A. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00091 · Cited by 41
“…et al., 2010; Kodam et al., 2010; Borbon and Erickson, 2011), uptake (Bales et al., 1997, 1999; Holtzman et al., 2000; Irizarry et al., 2000; Cao et al., 2006; Kim et al., 2009), and removal (Koldamova et al., 2005; Wahrle et al., 2005, 2008) causally influence APP processing and Aβ generation.”
BackgroundIntracellular cholesterol homeostasis and amyloid precursor protein processing
Burns, M. P., & Rebeck, G. W. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.03.004 · Cited by 39
Klotho an Autophagy Stimulator as a Potential Therapeutic Target for Alzheimer’s Disease: A Review
Fung, T., Iyaswamy, A., Sreenivasmurthy, S. G., Krishnamoorthi, S., Guan, X.-J., Zhu, Z., Su, C.-F., Liu, J., Kan, Y., Zhang, Y., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10030705 · Cited by 43
Honokiol Increases ABCA1 Expression Level by Activating Retinoid X Receptor Beta
Jung, C., Horike, H., Cha, B., Uhm, K., Yamauchi, R., Yamaguchi, T., Hosono, T., Iida, K., Woo, J., & Michikawa, M. (2010) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.33.1105 · Cited by 39
Regulation of Cerebral Cholesterol Metabolism in Alzheimer Disease
Reiss, A. B., & Voloshyna, I. (2012) · Journal of Investigative Medicine · doi:10.2310/jim.0b013e318246d973 · Cited by 38
“The ABCA1 level in these mice significantly modulated AA deposition.(90) The striking phenotype that these mice possess is a complete absence of thioflavine-SYpositive amyloid plaques, once again leading to the conclusion that increasing ABCA1 function may have a therapeutic effect on AD.”
BackgroundFitz, N. F., Tapias, V., Cronican, A. A., Castranio, E. L., Saleem, M., Carter, A. Y., Lefterova, M. I., Lefterov, I. M., & Koldamova, R. P. (2015) · Brain · doi:10.1093/brain/awv293 · Cited by 38
“In contrast, Abca1 overexpression in PDAPP mice decreases amyloid burden (Wahrle et al., 2008).”
BackgroundManavalan, A. P. C., Kober, A. C., Metso, J., Lang, I., Becker, T. M., Hasslitzer, K., Zandl‐Lang, M., Fanaee‐Danesh, E., Pippal, J. B., Sachdev, V., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.499129 · Cited by 37
“Apolipoproteins documented in the CSF and CNS are mainly apoE, apoA-I, apoA-IV, apoD, apoH, and apoJ, and the lipoproteins detected have a density resembling HDL in plasma (56, 57).”
BackgroundInfluentialLipid efflux mechanisms, relation to disease and potential therapeutic aspects
Castaño, D., Rattanasopa, C., Monteiro-Cardoso, V. F., Corlianò, M., Liu, Y., Zhong, A., Rusu, M., Liehn, E. A., & Singaraja, R. R. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.04.013 · Cited by 37
Apolipoprotein E isoform-dependent effects on the processing of Alzheimer's amyloid-β
Chai, A. B., Lam, H. H. J., Kockx, M., & Gelissen, I. C. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2021.158980 · Cited by 41
Cholesterol homeostasis regulated by ABCA1 is critical for retinal ganglion cell survival
Yang, J., Chen, Y., Zou, T., Bai, X., Yang, F., Wang, X., Huo, Y., Yan, B., Xu, Y., He, S., et al. (2022) · Science China Life Sciences · doi:10.1007/s11427-021-2126-2 · Cited by 37
“Generations of these genetically modified mice have been described previously (Hamon et al., 2000; Wahrle et al., 2008).”
Background
Metadata
- Authors
- Wahrle, S. E., Jiang, H., Parsadanian, M., Kim, J., Li, A., Knoten, A., Jain, S., Hirsch-Reinshagen, V., Wellington, C. L., Bales, K. R., Paul, S. M., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- University of British Columbia (CA)
- Eli Lilly (United States) (US)
- Corresponding author
- Holtzman, David M.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2008-01-17
- Volume
- 118
- Issue
- 2
- Pages
- 671-82
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2200302
- OpenAlex
- W2165895874
- Semantic Scholar
- d3897f2ef12c640d78228188112f4cc8ebffe747
- Cited by
- 370
- References
- 65
- Citations by year
- 2026: 4 · 2025: 15 · 2024: 16 · 2023: 15 · 2022: 20 · 2021: 24 · 2020: 22 · 2019: 17 · 2018: 13 · 2017: 20 · 2016: 14 · 2015: 24 · 2014: 33 · 2013: 25 · 2012: 30
- FWCI
- 15.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- American Health Assistance Foundation
- Eli Lilly and Company
- National Institutes of Health (AG13956)
- Canadian Institutes of Health Research
- National Institute on Aging (R01 AG013956, R37AG013956, AG13956)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK079333)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD047396, K08 HD047396)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- ABCA1, Alzheimer's disease, amyloid-beta deposition, amyloid plaques, apolipoprotein E, amyloid precursor protein overexpression, transgenic mice, dentate gyrus, cerebrospinal fluid, astrocytes, APOE genotype, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Astrocytes, Brain, Brain Chemistry, Disease Models, Animal, Lipoproteins, Male, Mice, Transgenic, Amyloid beta-Peptides, ATP-Binding Cassette Transporters, Mice, ATP Binding Cassette Transporter 1
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