The DOI matches its Crossref record; 66 of the 67 references it cites were found in a registry or an index; 47 of the 78 sources its claims cite were checked for support.
Human apoE Isoforms Differentially Regulate Brain Amyloid-β Peptide Clearance
Open accessAbstract
Human apoE4 increases the concentration of soluble Aβ in the brain by impairing its clearance.
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Claims the paper makes
26 Own result · 14 Own interpretation · 13 Partly supported · 10 Supported · 9 Own method · 5 Supported so far · 5 No full text of the sources · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset, sporadic Alzheimer’s disease (AD).”
- Also stated in: § Introduction · boosted
“The best established genetic risk factor for sporadic, late-onset AD is the apolipoprotein E (APOE) ε4 allele”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Abstract
What the sources say
- Not checked — no full text of the sourcecites [2] Corder EH Saunders AM Strittmatter WJ Schmechel DE Gaskell PC Small GW Roses AD Haines JL Pericak-Vance MA Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families Science 1993 261 921 923 8346443 source
- Partly supportedcites [3] Saunders AM Strittmatter WJ Schmechel D George-Hyslop PH Pericak-Vance MA Joo SH Rosi BL Gusella JF Crapper-MacLachlan DR Alberts MJ Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease Neurology 1993 43 1467 1472 8350998 sourceExperimental — accuracy not yet measured
The Abstract reports a significant association between APOE ε4 and sporadic Alzheimer’s disease, and the Statistical analysis section describes ε4 as a possible susceptibility gene or risk factor. Neither passage compares it with other genetic risk factors or establishes that it is the strongest. (LLM, conf=0.89)
- Not checked — no full text of the sourcecites [4] Corder EH Saunders AM Risch NJ Strittmatter WJ Schmechel DE Gaskell PC Jr. Rimmler JB Locke PA Conneally PM Schmader KE Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease Nat Genet 1994 7 180 184 7920638 source
- Partly supportedcites [5] Verghese PB Castellano JM Holtzman DM Apolipoprotein E in Alzheimer’s disease and other neurological disorders Lancet Neurol 2011 10 241 252 21349439 PMC3132088 sourceExperimental — accuracy not yet measured
The “APOE and Alzheimer’s disease” section identifies APOE as a risk gene for sporadic, late-onset AD and reports that ε4 raises risk substantially. The paper calls ε4 a major susceptibility factor, but our copy does not establish that it is the strongest genetic risk factor relative to other genes. (LLM, conf=0.83)
- Not checked — no full text of the sourcecites [46] Roses AD Apolipoprotein E alleles as risk factors in Alzheimer’s disease Annu Rev Med 1996 47 387 400 8712790 source
boostedcorrelational- 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.
- Also stated in: § Introduction · boosted
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
“in contrast, the APOE ε2 allele confers protection against developing AD (2-5).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Introduction
What the sources say
- Not checked — no full text of the sourcecites [2] Corder EH Saunders AM Strittmatter WJ Schmechel DE Gaskell PC Small GW Roses AD Haines JL Pericak-Vance MA Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families Science 1993 261 921 923 8346443 source
- Could not verifycites [3] Saunders AM Strittmatter WJ Schmechel D George-Hyslop PH Pericak-Vance MA Joo SH Rosi BL Gusella JF Crapper-MacLachlan DR Alberts MJ Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease Neurology 1993 43 1467 1472 8350998 sourceExperimental — accuracy not yet measured
The Abstract and Statistical analysis passages associate APOE ε4 with increased susceptibility to late-onset AD, but do not say that ε2 protects against developing AD. A search for ε2 allele frequencies and protective effects found only a passage describing how ε2 is identified in genotyping, not its relationship to AD risk. (LLM, conf=0.76)
- Not checked — no full text of the sourcecites [4] Corder EH Saunders AM Risch NJ Strittmatter WJ Schmechel DE Gaskell PC Jr. Rimmler JB Locke PA Conneally PM Schmader KE Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease Nat Genet 1994 7 180 184 7920638 source
- Supportedcites [5] Verghese PB Castellano JM Holtzman DM Apolipoprotein E in Alzheimer’s disease and other neurological disorders Lancet Neurol 2011 10 241 252 21349439 PMC3132088 source
The Summary states that APOE ε2 is associated with decreased AD risk. The “APOE and Alzheimer’s disease” section specifies that ε2 carriers have reduced risk of developing late-onset AD. Page numbers are not provided in our copy. (LLM, conf=0.95)
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.
Every source the paper cites for this claim was checked and supports it.
In the paper
“A recent study wherein apoE/Aβ complexes were microinjected into wildtype mouse brain revealed that Aβ bound to apoE4 is cleared more slowly than when Aβ is complexed to apoE3 or apoE2 (56).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Discussion
What the sources say
- Supportedcites [56] Deane R Sagare A Hamm K Parisi M Lane S Finn MB Holtzman DM Zlokovic BV apoE isoform-specific disruption of amyloid beta peptide clearance from mouse brain J Clin Invest 2008 118 4002 4013 19033669 PMC2582453 source
The Results state that Aβ clearance was inhibited most when complexed with apoE4, compared with apoE3 or apoE2. The Brain clearance studies section describes microinfusing Aβ–apoE complexes into the brains of C57BL/6 mice. Page numbers are unavailable in our copy. (LLM, conf=0.94)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The concentration of soluble Aβ in the ISF throughout life has been shown to be closely associated with the amount of Aβ that ultimately deposits in the extracellular space of the brain (29-31).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > Soluble Aβ concentration and clearance in brain ISF of old mice is human apoE isoform-dependent
What the sources say
- Partly supportedcites [29] Cirrito JR May PC O’Dell MA Taylor JW Parsadanian M Cramer JW Audia JE Nissen JS Bales KR Paul SM DeMattos RB Holtzman DM In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life J Neurosci 2003 23 8844 8853 14523085 PMC6740389 sourceExperimental — accuracy not yet measured
The ‘Relationships between ISF Aβ, CSF Aβ, and plaque load’ section reports a trend toward correlation between hippocampal ISF Aβ and plaque load in 12- to 15-month-old PDAPP mice; Figure 5 gives p = 0.1582. This does not establish a close association throughout life or show that ISF concentration predicts the amount ultimately deposited. Our copy provides no page number for these passages. (LLM, conf=0.88)
- Partly supportedcites [30] Yan P Bero AW Cirrito JR Xiao Q Hu X Wang Y Gonzales E Holtzman DM Lee JM Characterizing the appearance and growth of amyloid plaques in APP/PS1 mice J Neurosci 2009 29 10706 10714 19710322 PMC2756291 sourceExperimental — accuracy not yet measured
The Discussion links soluble ISF Aβ concentration to plaque growth in APP/PS1 mice and reports that brain regions with higher ISF Aβ early in life later develop plaque pathology. The Introduction says soluble Aβ is present throughout life, but the paper does not establish a close, lifelong association between its concentration and the total amount ultimately deposited. (LLM, conf=0.82)
- Partly supportedcites [31] Kim J Castellano JM Jiang H Basak JM Parsadanian M Pham V Mason SM Paul SM Holtzman DM Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance Neuron 2009 64 632 644 20005821 PMC2787195 sourceExperimental — accuracy not yet measured
The Results section reports that young LDLR-overexpressing mice had lower soluble ISF Aβ and that enhanced early-life clearance likely underlies their reduced Aβ accumulation with age. This supports an association between early ISF Aβ and later deposition in these mice, but the paper does not establish ISF concentrations throughout life or a close quantitative association with the amount ultimately deposited. (LLM, conf=0.84)
boostedcorrelational- 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“APOE status has been found to modulate the onset of extracellular amyloid plaque deposition, one of the key pathognomonic features of the disease (6, 7).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Introduction
What the sources say
- Partly supportedcites [6] Reiman EM Chen K Liu X Bandy D Yu M Lee W Ayutyanont N Keppler J Reeder SA Langbaum JB Alexander GE Klunk WE Mathis CA Price JC Aizenstein HJ DeKosky ST Caselli RJ Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease Proc Natl Acad Sci U S A 2009 106 6820 6825 19346482 PMC2665196 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports greater fibrillar amyloid-β burden in cognitively normal APOE ε4 carriers than in noncarriers, supporting an association between APOE status and deposition. It does not establish when plaque deposition begins or show that APOE status modulates its onset; the younger onset discussed in the paper concerns dementia, not deposition. (LLM, conf=0.86)
- Partly supportedcites [7] Morris JC Roe CM Xiong C Fagan AM Goate AM Holtzman DM Mintun MA APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging Ann Neurol 2010 67 122 131 20186853 PMC2830375 sourceExperimental — accuracy not yet measured
The Discussion reports that age and APOE genotype interact to affect the frequency of cerebral amyloid-β deposition in cognitively normal older adults, and the Results show genotype-dependent differences in deposition markers. This supports an effect on deposition with age, but the paper does not directly establish when extracellular plaques first appear in individuals of each genotype. (LLM, conf=0.82)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“we and others have reported human apoE isoform-dependent differences in amyloid plaque deposition in APP-transgenic mice (E4 > E3 > E2) (10-14).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Introduction
What the sources say
- Partly supportedcites [10] Holtzman DM Bales KR Tenkova T Fagan AM Parsadanian M Sartorius LJ Mackey B Olney J McKeel D Wozniak D Paul SM Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer’s disease Proc Natl Acad Sci U S A 2000 97 2892 2897 10694577 PMC16026 sourceExperimental — accuracy not yet measured
The Results section reports greater Aβ deposition and more fibrillar plaques in apoE4- than apoE3-expressing APP-transgenic mice. The Methods section describes comparisons of apoE3 and apoE4 mice, but not apoE2 mice; this paper therefore supports E4 > E3, not the full E4 > E3 > E2 ranking. Page numbers were not available in our copy. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [11] Fagan AM Watson M Parsadanian M Bales KR Paul SM Holtzman DM Human and murine ApoE markedly alters A beta metabolism before and after plaque formation in a mouse model of Alzheimer’s disease Neurobiol Dis 2002 9 305 318 11950276 source
- Partly supportedcites [12] Dodart JC Marr RA Koistinaho M Gregersen BM Malkani S Verma IM Paul SM Gene delivery of human apolipoprotein E alters brain Abeta burden in a mouse model of Alzheimer’s disease Proc Natl Acad Sci U S A 2005 102 1211 1216 15657137 PMC544620 sourceExperimental — accuracy not yet measured
The Results report greater hippocampal Aβ burden with apoE4 than apoE3 in PDAPP mice lacking mouse apoE, and lower burden with apoE2 than apoE3 in mice expressing mouse apoE. They do not establish the full E4 > E3 > E2 ordering for amyloid plaque deposition under the same conditions: apoE2 and apoE3 did not differ in the mice lacking mouse apoE, and apoE4 did not increase burden in mice expressing it. (LLM, conf=0.88)
- Partly supportedcites [13] Fryer JD Simmons K Parsadanian M Bales KR Paul SM Sullivan PM Holtzman DM Human apolipoprotein E4 alters the amyloid-beta 40:42 ratio and promotes the formation of cerebral amyloid angiopathy in an amyloid precursor protein transgenic model J Neurosci 2005 25 2803 2810 15772340 PMC6725147 sourceExperimental — accuracy not yet measured
The Results section and Figure 4 report greater parenchymal plaque deposition in 15-month-old APPsw mice expressing human apoE4 than in those expressing apoE3. The paper compares human apoE3 and apoE4, but does not test human apoE2, so it cannot establish the full E4 > E3 > E2 ranking. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [14] Bales KR Liu F Wu S Lin S Koger D DeLong C Hansen JC Sullivan PM Paul SM Human APOE isoform-dependent effects on brain beta-amyloid levels in PDAPP transgenic mice J Neurosci 2009 29 6771 6779 19474305 PMC6665579 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Several in vitro studies have demonstrated that lipidated apoE2 and apoE3 bind Aβ with greater affinity compared to apoE4 (39, 51-54).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Discussion
What the sources say
- Supportedcites [39] Kim J Basak JM Holtzman DM The role of apolipoprotein E in Alzheimer’s disease Neuron 2009 63 287 303 19679070 PMC3044446 source
The “In vitro Aβ binding studies” section reports that lipid-associated apoE2 and apoE3 form complexes with Aβ to a much greater extent than apoE4. It also says most studies find the binding-efficiency order apoE2 > apoE3 ≫ apoE4. No page number is provided in our copy. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [51] LaDu MJ Falduto MT Manelli AM Reardon CA Getz GS Frail DE Isoform-specific binding of apolipoprotein E to beta-amyloid J Biol Chem 1994 269 23403 23406 8089103 source
- Supportedcites [52] Yang DS Smith JD Zhou Z Gandy SE Martins RN Characterization of the binding of amyloid-beta peptide to cell culture-derived native apolipoprotein E2, E3, and E4 isoforms and to isoforms from human plasma J Neurochem 1997 68 721 725 9003062 source
The Discussion (page unavailable) reports that native apoE2 binds Aβ as avidly as apoE3, while apoE4 binds poorly or not at all in the in vitro assays. It says the pattern was also observed with native human-plasma apoE, and separately describes plasma apoE as lipid-associated. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [53] Aleshkov S Abraham CR Zannis VI Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian cells with amyloid peptide beta (1-40). Relevance to Alzheimer’s disease Biochemistry 1997 36 10571 10580 9265639 source
- Partly supportedcites [54] Tokuda T Calero M Matsubara E Vidal R Kumar A Permanne B Zlokovic B Smith JD Ladu MJ Rostagno A Frangione B Ghiso J Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer’s amyloid beta peptides Biochem J 2000 348 Pt 2 359 365 10816430 PMC1221074 sourceExperimental — accuracy not yet measured
The Results report significantly higher Aβ-binding affinity for lipidated apoE3 than for lipidated apoE4. The paper’s quantitative comparison covers apoE3 and apoE4, not apoE2, so it does not support the apoE2 portion of the claim. Page numbers are unavailable in our copy. (LLM, conf=0.88)
boostedcorrelational- 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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Because soluble ISF Aβ has been shown to closely reflect extracellular pools of Aβ (29-31)”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > Soluble Aβ concentration and clearance in brain ISF of old mice is human apoE isoform-dependent
What the sources say
- Supportedcites [29] Cirrito JR May PC O’Dell MA Taylor JW Parsadanian M Cramer JW Audia JE Nissen JS Bales KR Paul SM DeMattos RB Holtzman DM In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life J Neurosci 2003 23 8844 8853 14523085 PMC6740389 source
The Discussion identifies soluble ISF Aβ as a measurable brain Aβ pool and describes an extracellular Aβ pool in dynamic equilibrium between soluble and insoluble forms. The paper thus supports the claim that soluble ISF Aβ reflects extracellular Aβ, while distinguishing it from CSF and tissue-lysate measurements. (LLM, conf=0.86)
- Supportedcites [30] Yan P Bero AW Cirrito JR Xiao Q Hu X Wang Y Gonzales E Holtzman DM Lee JM Characterizing the appearance and growth of amyloid plaques in APP/PS1 mice J Neurosci 2009 29 10706 10714 19710322 PMC2756291 source
The Introduction identifies brain interstitial fluid (ISF) as the extracellular space into which Aβ is secreted and says Aβ is soluble there. The Methods describe directly measuring ISF Aβ by microdialysis, supporting the use of soluble ISF Aβ to represent extracellular Aβ in this context. The indexed passages provide no page numbers. (LLM, conf=0.88)
- Supportedcites [31] Kim J Castellano JM Jiang H Basak JM Parsadanian M Pham V Mason SM Paul SM Holtzman DM Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance Neuron 2009 64 632 644 20005821 PMC2787195 source
In the Results subsection on ISF Aβ, the paper states that soluble ISF Aβ is tightly correlated with total soluble Aβ in the brain’s extracellular pools. It also says that Aβ sampled by microdialysis likely reflects the extracellular pool more closely than Aβ measured from tissue homogenates. No page number is provided in our copy. (LLM, conf=0.94)
boostedcorrelational- 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Additionally, the APOE ε4 allele increases brain amyloid burden assessed by PIB-PET imaging in a gene dose-dependent manner (6).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > Biomarkers of cerebral Aβ deposition differ according to APOE genotype in humans
What the sources say
- Partly supportedcites [6] Reiman EM Chen K Liu X Bandy D Yu M Lee W Ayutyanont N Keppler J Reeder SA Langbaum JB Alexander GE Klunk WE Mathis CA Price JC Aizenstein HJ DeKosky ST Caselli RJ Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease Proc Natl Acad Sci U S A 2009 106 6820 6825 19346482 PMC2665196 sourceExperimental — accuracy not yet measured
The Results report that PiB-PET measures of fibrillar amyloid-β burden increased progressively with each additional APOE ε4 allele in the cognitively normal participants. The Discussion describes this as an association; the study does not establish that the allele causes amyloid burden to increase. (LLM, conf=0.84)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Given that a CSF Aβ42 concentration lower than 500 pg/mL has been utilized as a reliable threshold for the presence of cerebral Aβ deposition in humans (7, 19, 22, 26)”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > Biomarkers of cerebral Aβ deposition differ according to APOE genotype in humans
What the sources say
- Supportedcites [7] Morris JC Roe CM Xiong C Fagan AM Goate AM Holtzman DM Mintun MA APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging Ann Neurol 2010 67 122 131 20186853 PMC2830375 source
The Results use CSF Aβ42 <500 pg/mL as the threshold for an abnormal value and say it is very similar to an autopsy-indexed cutoff for neuritic plaque burden. The Interpretation states that reduced CSF Aβ42 appears to reflect cerebral Aβ deposition. The paper does not call the threshold ‘reliable’ in those words, but its use and comparison support the paraphrase. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [19] Fagan AM Roe CM Xiong C Mintun MA Morris JC Holtzman DM Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults Arch Neurol 2007 64 343 349 17210801 source
- Supportedcites [22] Fagan AM Head D Shah AR Marcus D Mintun M Morris JC Holtzman DM Decreased cerebrospinal fluid Abeta(42) correlates with brain atrophy in cognitively normal elderly Ann Neurol 2009 65 176 183 19260027 PMC2763631 source
The Results report using CSF Aβ42 below 500 pg/mL as a surrogate for brain amyloid. In the PET PIB-tested subset, the cutoff identified all PIB-positive individuals and had 83% specificity, supporting its description as a reliable threshold while not implying perfect accuracy. (LLM, conf=0.94)
- Partly supportedcites [26] Tapiola T Alafuzoff I Herukka SK Parkkinen L Hartikainen P Soininen H Pirttila T Cerebrospinal fluid {beta}-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain Arch Neurol 2009 66 382 389 19273758 sourceExperimental — accuracy not yet measured
The CSF Biomarker Levels and Amyloid Pathologic Changes section reports that lower CSF Aβ42 was associated with greater cerebral amyloid burden, but gives 515 pg/mL—not 500 pg/mL—as the optimum cutoff for pathologic neuritic plaques. The Comment section cautions that this cutoff was valid only in the study group and required independent validation, so the paper does not establish it as a reliable threshold in humans generally. Page numbers were not provided in our copy. (LLM, conf=0.89)
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.
- Supported
- Probably not a substantial claim. 25
- It may state two separate claims as one. 11
Every source the paper cites for this claim was checked and supports it.
In the paper
“One study found that antagonizing the apoE/Aβ interaction with a small peptide decreased Aβ pathology in the mouse brain”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Discussion
What the sources say
- Supportedcites [57] Sadowski MJ Pankiewicz J Scholtzova H Mehta PD Prelli F Quartermain D Wisniewski T Blocking the apolipoprotein E/amyloid-beta interaction as a potential therapeutic approach for Alzheimer’s disease Proc Natl Acad Sci U S A 2006 103 18787 18792 17116874 PMC1654132 source
The Discussion reports that the short synthetic peptide Aβ12-28P blocked apoE binding to Aβ and reduced Aβ deposits and total brain Aβ in two transgenic mouse models of Alzheimer's disease. This directly supports the claim. (LLM, conf=0.94)
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 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
“lipid-free apoE4 was found to facilitate Aβ fibrillization in vitro to a greater degree compared to apoE3 [(47, 48); see (39) for a review].”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Discussion
What the sources say
- Not checked — no full text of the sourcecites [47] Ma J Yee A Brewer HB Jr. Das S Potter H Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments Nature 1994 372 92 94 7969426 source
- Not checked — no full text of the sourcecites [48] Wisniewski T Castano EM Golabek A Vogel T Frangione B Acceleration of Alzheimer’s fibril formation by apolipoprotein E in vitro Am J Pathol 1994 145 1030 1035 7977635 PMC1887417
- Supportedcites [39] Kim J Basak JM Holtzman DM The role of apolipoprotein E in Alzheimer’s disease Neuron 2009 63 287 303 19679070 PMC3044446 source
The “In vitro Aβ aggregation studies” section reports that apoE4 promoted Aβ42 fibrillization more than the other isoforms and increased Aβ40 aggregation more efficiently than apoE3. The “Difference in apoE preparations” section says most in vitro studies used lipid-free apoE; it also cautions that other studies found conflicting results. (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.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the presence of which dramatically increases risk for developing AD and decreases age of onset by 10 to 15 years”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Introduction
What the sources say
- Not checked — no full text of the sourcecites [2] Corder EH Saunders AM Strittmatter WJ Schmechel DE Gaskell PC Small GW Roses AD Haines JL Pericak-Vance MA Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families Science 1993 261 921 923 8346443 source
- Partly supportedcites [3] Saunders AM Strittmatter WJ Schmechel D George-Hyslop PH Pericak-Vance MA Joo SH Rosi BL Gusella JF Crapper-MacLachlan DR Alberts MJ Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease Neurology 1993 43 1467 1472 8350998 sourceExperimental — accuracy not yet measured
The Abstract and Results report a significant association between APOE ε4 and late-onset familial and sporadic AD, supporting the increased-risk portion of the claim. They do not report that ε4 decreases age of onset by 10–15 years; the discussion instead links earlier onset to APP mutations. Passage page numbers are not provided in our copy. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [4] Corder EH Saunders AM Risch NJ Strittmatter WJ Schmechel DE Gaskell PC Jr. Rimmler JB Locke PA Conneally PM Schmader KE Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease Nat Genet 1994 7 180 184 7920638 source
- Partly supportedcites [5] Verghese PB Castellano JM Holtzman DM Apolipoprotein E in Alzheimer’s disease and other neurological disorders Lancet Neurol 2011 10 241 252 21349439 PMC3132088 sourceExperimental — accuracy not yet measured
The “APOE and Alzheimer’s disease (AD)” section reports that one or two copies of APOE ε4 increase late-onset AD risk approximately 3- or 12-fold and shift onset earlier by approximately one to two decades relative to non-carriers. This supports the risk and earlier-onset claims, but the paper gives a 10–20-year range, not the more specific 10–15 years attributed to it. (LLM, conf=0.83)
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.
Every source the paper cites for this claim was checked and supports it.
In the paper
“perhaps suggesting the extracted pools we measured do not completely reflect the ISF pool of Aβ (31, 38).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > ApoE isoform-dependent differences in Aβ concentration and clearance exist before Aβ deposition
What the sources say
- Supportedcites [31] Kim J Castellano JM Jiang H Basak JM Parsadanian M Pham V Mason SM Paul SM Holtzman DM Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance Neuron 2009 64 632 644 20005821 PMC2787195 source
The Results section reports that conventional biochemical measurements did not show the Aβ change detected by ISF microdialysis. It explains that microdialysis likely reflects the extracellular pool more closely than total Aβ measured from tissue homogenates, supporting the citing sentence’s tentative distinction between extracted pools and ISF Aβ. (LLM, conf=0.89)
- Supportedcites [38] Kang JE Lim MM Bateman RJ Lee JJ Smyth LP Cirrito JR Fujiki N Nishino S Holtzman DM Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle Science 2009 326 1005 1007 19779148 PMC2789838 source
The passage labeled Abstract reports that ISF Aβ fluctuated between dark and light periods while Aβ in total hippocampal tissue homogenates did not differ significantly. It concludes that the ISF pool is likely regulated independently of total intracellular and membrane-associated Aβ, supporting the citing sentence’s tentative distinction between extracted and ISF pools. (LLM, conf=0.90)
hedged- 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
“For example, using in vivo stable isotopic labeling kinetics, our group recently reported that CSF Aβ clearance and not synthesis is impaired in a small cohort of late-onset AD patients, though the effect of APOE genotype was not assessed (65).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Discussion
What the sources say
- Supportedcites [65] Mawuenyega KG Sigurdson W Ovod V Munsell L Kasten T Morris JC Yarasheski KE Bateman RJ Decreased Clearance of CNS {beta}-Amyloid in Alzheimer’s Disease Science 2010 PMC3073454 21148344 source
The results passage (page not provided) reports slower Aβ42 and Aβ40 clearance in AD than in controls, with no difference in production rates; the limitations passage specifies twelve participants per group. The paper describes metabolic labeling and late-onset AD. It mentions ApoE4 as a possible mechanism but reports no assessment of genotype effects. (LLM, conf=0.88)
plain- 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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“we determined the percentage of area occupied by immunoreactive Aβ or amyloid (X-34-positive signal) in a blinded fashion”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Materials and Methods > Tissue preparation and quantification of Aβ/amyloid burden
What the sources say
- Supportedcites [31] Kim J Castellano JM Jiang H Basak JM Parsadanian M Pham V Mason SM Paul SM Holtzman DM Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance Neuron 2009 64 632 644 20005821 PMC2787195 source
The Experimental Procedures section, “Quantitative Analyses of Amyloid Deposition” (page not available), describes quantifying anti-Aβ-stained and X-34-stained brain sections to assess plaque load. It explicitly states that all analyses were performed in a blinded manner. (LLM, conf=0.91)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Several studies have indicated that apoE concentration varies by human apoE isoform (39)”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > ApoE isoform-dependent differences in Aβ concentration and clearance exist before Aβ deposition
What the sources say
- Partly supportedcites [39] Kim J Basak JM Holtzman DM The role of apolipoprotein E in Alzheimer’s disease Neuron 2009 63 287 303 19679070 PMC3044446 sourceExperimental — accuracy not yet measured
The ‘CSF apoE levels among isoforms’ section reports one human study finding different apoE4 proportions in CSF and plasma, but also says several human studies found no significant CSF concentration differences. The ‘Levels of apoE isoforms in the brain parenchyma’ section describes human findings as controversial. Thus the review supports evidence of isoform-related variation, but not an unqualified account of several consistent human findings. (LLM, conf=0.84)
hedgedcorrelational- 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A preponderance of evidence supports the interpretation that PIB uptake and CSF Aβ42 are reliable surrogate markers of amyloid plaque pathology in living subjects (15-19).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > Biomarkers of cerebral Aβ deposition differ according to APOE genotype in humans
What the sources say
- Not checked — no full text of the sourcecites [15] Rowe CC Ng S Ackermann U Gong SJ Pike K Savage G Cowie TF Dickinson KL Maruff P Darby D Smith C Woodward M Merory J Tochon-Danguy H O’Keefe G Klunk WE Mathis CA Price JC Masters CL Villemagne VL Imaging beta-amyloid burden in aging and dementia Neurology 2007 68 1718 1725 17502554 source
- Partly supportedcites [16] Jack CR Jr. Lowe VJ Senjem ML Weigand SD Kemp BJ Shiung MM Knopman DS Boeve BF Klunk WE Mathis CA Petersen RC 11C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment Brain 2008 131 665 680 18263627 PMC2730157 sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) describes PiB as an in vivo amyloid-plaque tracer whose binding corresponds to plaque distribution. It also reports an inverse correlation between cortical PiB uptake and CSF Aβ42, but does not establish that CSF Aβ42 is itself a reliable surrogate for plaque pathology. The Discussion (page unavailable) calls PiB an accurate marker of brain fibrillar amyloid a current expectation. (LLM, conf=0.83)
- Partly supportedcites [17] Shaw LM Vanderstichele H Knapik-Czajka M Clark CM Aisen PS Petersen RC Blennow K Soares H Simon A Lewczuk P Dean R Siemers E Potter W Lee VM Trojanowski JQ Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects Ann Neurol 2009 65 403 413 19296504 PMC2696350 sourceExperimental — accuracy not yet measured
The Interpretation section links reduced CSF Aβ1-42 to amyloid accumulation in brain plaques, and the Discussion reports that CSF Aβ1-42 was the most sensitive single AD biomarker in the studied cohorts. The paper mentions Pittsburgh compound B imaging in Subjects and Methods but does not establish that PIB uptake is a reliable surrogate for plaque pathology. Page numbers are not available in our copy. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [18] Fagan AM Mintun MA Mach RH Lee SY Dence CS Shah AR LaRossa GN Spinner ML Klunk WE Mathis CA DeKosky ST Morris JC Holtzman DM Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans Ann Neurol 2006 59 512 519 16372280 source
- Not checked — no full text of the sourcecites [19] Fagan AM Roe CM Xiong C Mintun MA Morris JC Holtzman DM Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults Arch Neurol 2007 64 343 349 17210801 source
boostedcorrelational- 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 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
“On the basis of previous studies (7, 27), individuals with mean cortical binding potential (MCBP) for PIB >0.18 were considered PIB-positive (PIB+).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > Biomarkers of cerebral Aβ deposition differ according to APOE genotype in humans
What the sources say
- Supportedcites [7] Morris JC Roe CM Xiong C Fagan AM Goate AM Holtzman DM Mintun MA APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging Ann Neurol 2010 67 122 131 20186853 PMC2830375 source
The Results, under “Unadjusted data” (page not provided), explicitly define PIB-positive individuals as those with MCBP > 0.18. (LLM, conf=0.95)
- Not checked — no full text of the sourcecites [27] Mintun MA Larossa GN Sheline YI Dence CS Lee SY Mach RH Klunk WE Mathis CA DeKosky ST Morris JC [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease Neurology 2006 67 446 452 16894106 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.
Probably not a substantial claim.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Because changes in apoE and Aβ metabolism in the brain ISF early in life can markedly alter Aβ deposition later in life (31, 32)”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > ApoE isoform-dependent differences in Aβ concentration and clearance exist before Aβ deposition
What the sources say
- Supportedcites [31] Kim J Castellano JM Jiang H Basak JM Parsadanian M Pham V Mason SM Paul SM Holtzman DM Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance Neuron 2009 64 632 644 20005821 PMC2787195 source
The Results section reports that LDLR overexpression lowered brain apoE levels and increased Aβ elimination from the ISF of young mice. It concludes that this early increase in Aβ elimination likely underlies the marked reduction in Aβ accumulation as the mice age. The claim’s “can” is consistent with that qualified conclusion (page numbers unavailable in our copy). (LLM, conf=0.90)
- Supportedcites [32] DeMattos RB Cirrito JR Parsadanian M May PC O’Dell MA Taylor JW Harmony JA Aronow BJ Bales KR Paul SM Holtzman DM ApoE and clusterin cooperatively suppress Abeta levels and deposition: evidence that ApoE regulates extracellular Abeta metabolism in vivo Neuron 2004 41 193 202 14741101 source
The Abstract reports elevated brain ISF Aβ in apoE-deficient mice and earlier, markedly increased Aβ deposition in apoE/clusterin double-knockout mice. It also reports altered Aβ levels at 3 months, before deposition, and greater deposition at 6 and 12 months. This supports the claim in the paper’s PDAPP mouse model. (LLM, conf=0.89)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Since the metabolite urea has been utilized as an independent measure of probe function and recovery in both human and animal brain microdialysis studies (34-37)”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > ApoE isoform-dependent differences in Aβ concentration and clearance exist before Aβ deposition
What the sources say
- Not checked — no full text of the sourcecites [34] Ronne-Engstrom E Cesarini KG Enblad P Hesselager G Marklund N Nilsson P Salci K Persson L Hillered L Intracerebral microdialysis in neurointensive care: the use of urea as an endogenous reference compound J Neurosurg 2001 94 397 402 11235942 source
- Not checked — no full text of the sourcecites [35] Hillered L Vespa PM Hovda DA Translational neurochemical research in acute human brain injury: the current status and potential future for cerebral microdialysis J Neurotrauma 2005 22 3 41 15665601 source
- Partly supportedcites [36] Brody DL Magnoni S Schwetye KE Spinner ML Esparza TJ Stocchetti N Zipfel GJ Holtzman DM Amyloid-beta dynamics correlate with neurological status in the injured human brain Science 2008 321 1221 1224 18755980 PMC2577829 sourceExperimental — accuracy not yet measured
The paper’s main text (indexed under Abstract; page unavailable) reports using urea concentrations in human brain microdialysis samples to check the stability of catheter function. It does not describe urea use in animal studies or use urea to estimate probe recovery; it estimates Aβ recovery by in vitro experiments and zero-flow extrapolation instead. (LLM, conf=0.88)
- Supportedcites [37] Schwetye KE Cirrito JR Esparza TJ Donald C. L. Mac Holtzman DM Brody DL Traumatic brain injury reduces soluble extracellular amyloid-beta in mice: a methodologically novel combined microdialysis-controlled cortical impact study Neurobiol Dis 2010 40 555 564 20682338 PMC2955836 source
The Results section (‘Measurements of Aβ1-x likely reflect physiological sequelae of TBI’; page not supplied) says urea recovery was used as a control for probe function in this mouse study and that urea is frequently used for that purpose in human cerebral microdialysis. The Methods (‘Urea assay’; page not supplied) also says experiments with abnormal urea levels were excluded for probe malfunction. (LLM, conf=0.93)
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.
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
“the [11C]-benzothiazole radiotracer, Pittsburgh Compound B (PIB), as well as other tracers, can bind to fibrillar Aβ plaques, allowing for visualization of brain amyloid in individuals during positron emission tomography (PET) (23-25).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > Biomarkers of cerebral Aβ deposition differ according to APOE genotype in humans
What the sources say
- Not checked — no full text of the sourcecites [23] Klunk WE Engler H Nordberg A Wang Y Blomqvist G Holt DP Bergstrom M Savitcheva I Huang GF Estrada S Ausen B Debnath ML Barletta J Price JC Sandell J Lopresti BJ Wall A Koivisto P Antoni G Mathis CA Langstrom B Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B Ann Neurol 2004 55 306 319 14991808 source
- Supportedcites [24] Ikonomovic MD Klunk WE Abrahamson EE Mathis CA Price JC Tsopelas ND Lopresti BJ Ziolko S Bi W Paljug WR Debnath ML Hope CE Isanski BA Hamilton RL DeKosky ST Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease Brain 2008 131 1630 1645 18339640 PMC2408940 source
The Introduction describes PET imaging of amyloid deposits using amyloid-binding compounds, including PiB, and states that PiB preferentially binds Aβ fibrils. The Discussion also links PiB-bound Aβ plaques to the in vivo PET signal. Together, these passages support the claim about PiB and other amyloid-binding tracers. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [25] Leinonen V Alafuzoff I Aalto S Suotunen T Savolainen S Nagren K Tapiola T Pirttila T Rinne J Jaaskelainen JE Soininen H Rinne JO Assessment of beta-amyloid in a frontal cortical brain biopsy specimen and by positron emission tomography with carbon 11-labeled Pittsburgh Compound B Arch Neurol 2008 65 1304 1309 18695050 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.
Probably not a substantial claim.
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
“Theoretically, the maximum in vivo steady state concentration of an analyte being dialyzed exists at the point at which there is no flow of the perfusion buffer (31, 33).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > ApoE isoform-dependent differences in Aβ concentration and clearance exist before Aβ deposition
What the sources say
- Supportedcites [31] Kim J Castellano JM Jiang H Basak JM Parsadanian M Pham V Mason SM Paul SM Holtzman DM Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance Neuron 2009 64 632 644 20005821 PMC2787195 source
The Results section states that the theoretical in vivo steady-state concentration of a dialyzed analyte is obtained at zero perfusion-buffer flow. The authors varied the flow rate and extrapolated to zero flow to estimate that concentration; the claim’s use of “maximum” is consistent with that account. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [33] Menacherry S Hubert W Justice JB Jr. In vivo calibration of microdialysis probes for exogenous compounds Anal Chem 1992 64 577 583 1580357 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.
Probably not a substantial claim.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“thresholding each slide to minimize false-positive signal, as described (31)”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Materials and Methods > Tissue preparation and quantification of Aβ/amyloid burden
What the sources say
- Supportedcites [31] Kim J Castellano JM Jiang H Basak JM Parsadanian M Pham V Mason SM Paul SM Holtzman DM Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance Neuron 2009 64 632 644 20005821 PMC2787195 source
The Experimental Procedures section (Quantitative Analyses of Amyloid Deposition; page not provided) says scanned section images were thresholded and each identified object was inspected to determine whether it was a plaque. That describes thresholding with a check against false-positive plaque detections, although the paper phrases the thresholding step as highlighting plaques. (LLM, conf=0.86)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“because the extent of apoE lipidation may also play a role in modulating Aβ accumulation (41)”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > ApoE isoform-dependent differences in Aβ concentration and clearance exist before Aβ deposition
What the sources say
- Supportedcites [41] Wahrle SE Jiang H Parsadanian M Kim J Li A Knoten A Jain S Hirsch-Reinshagen V Wellington CL Bales KR Paul SM Holtzman DM Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease J Clin Invest 2008 118 671 682 18202749 PMC2200302 source
The Discussion reports that ABCA1 overexpression increased apoE lipidation and reduced Aβ deposition in PDAPP mice. It also proposes that highly lipidated apoE may alter Aβ clearance or aggregation. This supports the claim’s cautious wording that the extent of apoE lipidation may modulate Aβ accumulation. (LLM, conf=0.94)
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.
- Supported
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
“Whereas apoE levels from brain homogenates were higher in PDAPP/E2 mice compared to PDAPP/E3 or PDAPP/E4 mice, levels did not differ between PDAPP/E3 and PDAPP/E4 mice (Fig. S4B).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > ApoE isoform-dependent differences in Aβ concentration and clearance exist before Aβ deposition
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.
- Rests on an assumption: The PDAPP/TRE mouse lines expressing different human apoE isoforms are on identical genetic backgrounds except for the APOE transgene.
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
“Neither the levels of phosphate-buffered saline (PBS)-soluble Aβ40 nor the levels of murine APP in hippocampal lysates from young apoE knock-in mice expressing murine APP differed according to apoE isoform”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > ApoE isoform-dependent differences in Aβ concentration and clearance exist before Aβ deposition
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
“The concentration of apoE in the CSF was also significantly lower in APOE ε4-carriers (individuals with one or two copies of APOE ε4) compared to APOE ε3/ε3 individuals, but the concentration of apoE did not differ between those who were APOE ε3/ε3 and those who were APOE ε4/ε4.”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > ApoE isoform-dependent differences in Aβ concentration and clearance exist before Aβ deposition
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.
- Rests on an assumption: The human cohort of cognitively normal individuals younger than 70 is free of confounding by preclinical AD dementia.
- Rests on an assumption: The APOE genotype groups in the human cohort are comparable in all relevant AD risk factors except APOE.
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
“Because the kinetics of the reaction for all samples were reliably linear in the 20- to 60-min interval”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Materials and Methods > Biochemical analyses of hippocampal homogenates from young PDAPP/TRE mice
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
“we cannot exclude the possibility that apoE isoforms also modulate Aβ accumulation by directly facilitating Aβ fibrillization.”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Discussion
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.
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 observation has prompted some to hypothesize that the stronger interaction between Aβ and apoE2 or apoE3 relative to apoE4 may result in greater Aβ clearance, consistent with the clearance pattern we observed in vivo in the current study.”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Discussion
hedgedconditional- Asserted: fails — The authors may not 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 authors may not put it forward as true. The paper’s conclusions may not depend on it. 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
“The concentration of urea did not differ among groups, suggesting that probe function was equivalent across experiments in PDAPP/TRE mice (Fig. S1C).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > ApoE isoform-dependent differences in Aβ concentration and clearance exist before Aβ deposition
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.
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, these results suggest that whereas higher apoE concentration in the context of apoE2 may underlie more rapid Aβ clearance relative to apoE4, apoE concentration is unlikely to underlie Aβ clearance differences observed in the context of apoE3 versus apoE4.”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > ApoE isoform-dependent differences in Aβ concentration and clearance exist before Aβ deposition
hedgedconditional- 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
“One recent in vitro study found that human apoE isoforms differed in their ability to facilitate neprilysin-mediated degradation of Aβ42 within microglia, with apoE4 being the least effective in facilitating Aβ degradation compared to apoE2 or apoE3 (60).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Discussion
What the sources say
- Not checked — no full text of the sourcecites [60] Jiang Q Lee CY Mandrekar S Wilkinson B Cramer P Zelcer N Mann K Lamb B Willson TM Collins JL Richardson JC Smith JD Comery TA Riddell D Holtzman DM Tontonoz P Landreth GE ApoE promotes the proteolytic degradation of Abeta Neuron 2008 58 681 693 18549781 PMC2493297 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.
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, these results strongly suggest that the reduced clearance of Aβ from the brain ISF of PDAPP/E4 mice contributes to the increased concentration of Aβ in the ISF, likely resulting in earlier Aβ/amyloid plaque deposition.”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > ApoE isoform-dependent differences in Aβ concentration and clearance exist before Aβ deposition
boostedconditional- 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
“All animal procedures were performed according to protocols accepted by the Animal Studies Committee at Washington University School of Medicine.”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Materials and Methods > Animals
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
“which was calibrated with a standard curve of Aβ secreted from H4 APP695ΔNL neuroglioma cells”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Materials and Methods > In vivo stable isotopic labeling kinetics
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.
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
“All procedures were approved by Washington University’s Human Protection Office and written informed consent was obtained from all participants prior to study entry.”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Materials and Methods > CSF Aβ42, apoE, and PIB-PET assessment in humans
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. 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
“Loading was normalized by stripping blots and re-probing with α-tubulin antibody (Sigma).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Materials and Methods > Biochemical analyses of hippocampal homogenates from young PDAPP/TRE mice
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.
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
“Specificity of β-secretase activity was validated using a commercially available β-secretase inhibitor.”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Materials and Methods > Biochemical analyses of hippocampal homogenates from young PDAPP/TRE mice
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
“Positive controls for the six possible APOE genotypes were included on the genotyping plate.”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Materials and Methods > CSF Aβ42, apoE, and PIB-PET assessment in humans
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.
In the paper
“Overall, our results in PDAPP/TRE mice are consistent with a previous in vitro study showing no effect of apoE isoforms on APP processing (42).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > Amyloidogenic processing of APP does not vary according to human apoE isoform
What the sources say
- Not checked — no full text of the sourcecites [42] Biere AL Ostaszewski B Zhao H Gillespie S Younkin SG Selkoe DJ Co-expression of beta-amyloid precursor protein (betaAPP) and apolipoprotein E in cell culture: analysis of betaAPP processing Neurobiol Dis 1995 2 177 187 9174001 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.
In the paper
“we adapted an in vivo stable isotopic labeling kinetics technique previously described in humans (43).”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Results > Rates of Aβ synthesis do not differ according to human apoE isoform
What the sources say
- Not checked — no full text of the sourcecites [43] Bateman RJ Munsell LY Morris JC Swarm R Yarasheski KE Holtzman DM Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo Nat Med 2006 12 856 861 16799555 PMC2983090 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.
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 with our present results, the isoform-dependent pattern of apoE concentration in humans and in mice raises the possibility that apoE concentration alone may play a role in the pattern of Aβ clearance and subsequent Aβ accumulation”
§ Human apoE isoforms differentially regulate brain amyloid-β peptide clearance > Discussion
hedgedconditional- 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 paper relies on this without support.
The PDAPP/TRE mouse lines expressing different human apoE isoforms are on identical genetic backgrounds except for the APOE transgene.
“we used PDAPP mice in which human apoE isoforms are expressed under control of the mouse regulatory elements (PDAPP/TRE) (14).”
The paper relies on this without support.
The human cohort of cognitively normal individuals younger than 70 is free of confounding by preclinical AD dementia.
“we analyzed a cohort of cognitively normal individuals younger than age 70, an age after which the presence of AD dementia may confound the analyses.”
The paper relies on this without support.
The APOE genotype groups in the human cohort are comparable in all relevant AD risk factors except APOE.
“Although various demographic features of our cohort, such as age, sex, and education level, did not differ by APOE genotype”
The paper relies on this without support.
The mouse model of human apoE-dependent β-amyloidosis is a valid model for human Aβ clearance.
“Using a mouse model of human apoE-dependent β-amyloidosis, our present results may be directly relevant to human studies.”
The paper relies on this without support.
LY411,575 is a selective γ-secretase inhibitor that effectively blocks Aβ production.
“a selective γ-secretase inhibitor (LY411,575)”
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 cited source doesn’t support the claim as written.
In the citing paper
“Even in homozygous APOE2/2 mice, prior reports have been inconsistent regarding further reductions in amyloid pathology compared with APOE3/3 , re fl ecting ongoing debate 34,48,49 .”
From APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease (2026) · cites this paper as [34]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe claim comes from somewhere else, not from this source.
In the citing paper
“Because APOE4 is also a risk factor for cerebral amyloid angiopathy (CAA)31, we measured CAA before and after the inducible, astrocyte-specific transition to APOE2.”
From APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition (2025) · cites this paper as [31]
Checked by a reasoning model — may be wrong.
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
“APOE4 is associated with increased amyloid-β deposition, hyperphosphorylation and aggregation of tau, and accelerated cognitive decline4–7.”
From APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes (2022) · cites this paper as [6]
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
“Crossing a transgenic mouse model of AD that has high levels of human Aβ in the brain with human APOE targeted replacement mice demonstrated age-dependent and APOE isoform-dependent (E4>>E3>E2) Aβ deposition and amyloid burden in the brain in a manner that recapitulates the human condition observed in pre-symptomatic elderly APOE4 carriers as well as AD patients.18–21”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [19]
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
“while viral APOE2 delivery, APOE2 gene therapy, and inducible APOE4 to APOE2 switching have demonstrated that increasing APOE2 expression or replacing APOE4 with APOE2 can ameliorate AD-related phenotypes 7,8,33,34 .”
From APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease (2026) · cites this paper as [34]
Experimental — accuracy not yet measured
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
“Using homozygous human APOE knock-in mice, previous work demonstrated that APOE4 promotes A β aggregation and impairs its clearance relative to APOE3 34,38,39 .”
From APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease (2026) · cites this paper as [34]
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
“Previous work established that human APOE affects amyloid plaque deposition in the 5xFAD brain in a genotype-dependent fashion (E4 > E2)31.”
From APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition (2025) · cites this paper as [31]
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
“and in animal models, APOE4 compared with APOE3 and APOE2 leads to impaired clearance of A 𝛃 across the BBB (58, 98, 135) and an early BBB breakdown and transporters' dysregulation (9, 60, 85, 437).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [98]
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
“Moreover, the aggregated Aβ could activate microglia and induce the secretion of proinflammatory cytokines, which further induced Aβ aggregation and neuronal death.[ 24 ]”
From Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit (2021) · 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
“multiple lines of human and animal data clearly demonstrate that there is an isoform-specific difference in amyloid β clearance and accumulation [4,5].”
From Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease (2017) · cites this paper as [5]
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
“It is well established that the amyloid β accumulation in human brain follows the pattern of ApoE4 > ApoE3 > ApoE2 [5].”
From Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease (2017) · cites this paper as [5]
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
“ApoE isoforms encoded by various APOE alleles differentially influence the rate of soluble Aβ clearance from the brain interstitial space and formation of Aβ parenchymal plaques and VAβ [32, 33].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [32]
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 fact increased rate of soluble Aβ clearance across the BBB has been experimentally confirmed in the setting of the APOE ε2 allele [32, 48].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [32]
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
“Our studies suggest that the main effect of apoE on risk for AD is via its effect on Aβ clearance and aggregation (Castellano et al., 2011; Kim et al., 2009b; 2011; 2012a; Liao et al., 2014).”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as Castellano et al., 2011
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 far, the differential effect of targeted ApoE isoform replacement on Ab pathology has been reproduced in single APP V717F mice, which had to be at least 18 months of age to observe substantial Ab load.56,57”
From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [57]
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
“and to impair its clearance from the brain interstitial fluid (6).”
From Therapeutic Idol reduction ameliorates amyloidosis and improves cognitive function in APP/PS1 mice (2020) · cites this paper as [6]
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
“Although the mechanisms are not fully elucidated, apoE appears to influence AD at least in part by promoting amyloid-β (Aβ) aggregation and reducing Aβ clearance (Castellano et al., 2011; Huynh et al., 2017; Liu et al., 2017).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Castellano et al., 2011
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“To date, substantial evidence has demonstrated ApoE affects amyloid-β deposition in a dosage and isoform-specific fashion (ApoE4>ApoE3>ApoE2)96–100”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [100]
The cited source says what the claim attributes to it.
In the citing paper
“Previous studies using homozygous APOE knock-in mice have been essential for de fi ning isoform-speci fi c effects of APOE2 , APOE3 , and APOE4”
From APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease (2026) · cites this paper as [34]
The cited source says what the claim attributes to it.
In the citing paper
“APOE exerts toxic effects on the cerebrovascular system (694) and neurons (383, 384) and influences A 𝛃 clearance (60, 64, 98, 135, 256, 266, 278, 294, 315, 693), amyloid deposition (39, 256, 258, 266, 278, 314, 518, 612), and tau-related neurodegeneration (533) in an allele-dependent manner APOE4 > APOE3 > APOE2 .”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [98]
The cited source says what the claim attributes to it.
In the citing paper
“Evidence suggests that the effect of apoE isoforms on amyloid-β (Aβ) accumulation in the brain plays a critical role in AD pathogenesis.”
From Haploinsufficiency of Human APOE Reduces Amyloid Deposition in a Mouse Model of Amyloid-β Amyloidosis (2011) · cites this paper as Castellano et al., 2011
The cited source says what the claim attributes to it.
In the citing paper
“Like in humans, apoE4 expression in animal models that develop Aβ-amyloidosis results in greater Aβ and amyloid deposition than with apoE3 expression.”
From Haploinsufficiency of Human APOE Reduces Amyloid Deposition in a Mouse Model of Amyloid-β Amyloidosis (2011) · cites this paper as Castellano et al., 2011
The cited source says what the claim attributes to it.
In the citing paper
“Several studies demonstrated that apoE isoforms can differentially affect Aβ clearance (Deane et al., 2008; Jiang et al., 2008; Castellano et al., 2011).”
From Haploinsufficiency of Human APOE Reduces Amyloid Deposition in a Mouse Model of Amyloid-β Amyloidosis (2011) · cites this paper as Castellano et al., 2011
The cited source says what the claim attributes to it.
In the citing paper
“These striking differences in the brain levels of soluble Aβx-40 and Aβx-42 peptides, and the reversed ratio, between APP/E2 and APP/E4 mice are likely related to the well-established differential effect of apoE2 and apoE4 isoforms on Aβ brain clearance [28].”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [28]
The cited source says what the claim attributes to it.
In the citing paper
“Clearance of soluble Aβ from the brain is critical in preventing its accumulation and there is evidence this process can be differentially regulated by apoE isoforms [28].”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [28]
The cited source says what the claim attributes to it.
In the citing paper
“APOE genotype critically affects the burden of Aβ pathology in sporadic AD.”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [32]
The cited source says what the claim attributes to it.
In the citing paper
“suggesting that APOE alleles contribute to human AD risk by differentially regulating clearance of A 𝛃 from the brain”
From Therapeutic Idol reduction ameliorates amyloidosis and improves cognitive function in APP/PS1 mice (2020) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“A 𝛃 turnover and clearance in the mouse brain in vivo is strongly dependent upon ApoE isoform (6)”
From Therapeutic Idol reduction ameliorates amyloidosis and improves cognitive function in APP/PS1 mice (2020) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“Indeed, APOE has been shown to regulate extracellular Aβ metabolism independently of Aβ synthesis, and APOE isoforms differentially influence the clearance of soluble Aβ from the brain (Castellano et al., 2011; DeMattos et al., 2004).”
From Isogenic human stem cell models reveal mutation-dependent protective mechanisms of APOE3 Christchurch (2026) · cites this paper as Castellano et al., 2011
The cited source says what the claim attributes to it.
In the citing paper
“suggesting the distinct biochemical interactions influencing Aβ deposition or clearance [2, 3, 22, 23].”
From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [22]
The cited source says what the claim attributes to it.
In the citing paper
“APOE4-targeted replacement mice, expressing the human APOE4 allele instead of the mouse Apoe, crossed with different AD mouse models such as PDAPP, APP/ PS1ΔE9 and 5xFAD, accelerated plaque formation compared to APOE3-targeted replacement mice (Bales et al, 2009; Castellano et al, 2011; Fagan et al, 2002; Holtzman et al, 2000a; Rodriguez et al, 2014; Youmans et al, 2012).”
From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Castellano et al, 2011
The cited source says what the claim attributes to it.
In the citing paper
“In general, experiments suggest the order of APOE4 > APOE3 > APOE2 for effects on amyloid deposition (Fagan et al, 2002; Castellano et al, 2011; Hudry et al, 2013; Zhao et al, 2016)”
From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Castellano et al, 2011
The cited source says what the claim attributes to it.
In the citing paper
“we recently provided direct in vivo evidence that human apoE isoforms differentially regulate soluble Aβ clearance from brain interstitial fluid (ISF) (11), strongly suggesting that APOE's role in AD risk development is related to its regulation of Aβ clearance pathways.”
From Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood Aβ clearance in a mouse model of β-amyloidosis (2012) · cites this paper as [11]
The cited source says what the claim attributes to it.
In the citing paper
“While APOE4 decreases Aβ clearance without affecting Aβ production (8)”
From APOE4-mediated amyloid-β pathology depends on its neuronal receptor LRP1 (2019) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“Moreover, a second mechanism by which impaired ApoE4-containing vesicle recycling would be predicted to contribute to accelerated amyloid accumulation and plaque deposition (Fagan et al., 2002) involves the reduced turnover rate of Aβ in the brains of ApoE4 targeted replacement mice (Castellano et al., 2011) and humans (Wildsmith et al., 2012).”
From Reversal of ApoE4-induced recycling block as a novel prevention approach for Alzheimer’s disease (2018) · cites this paper as Castellano et al., 2011
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Consistent with APOE’s biological function2–6, APOE4 significantly altered signaling pathways associated with cholesterol homeostasis and transport.”
From APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes (2022) · cites this paper as [6]
Experimental — accuracy not yet measuredIn the citing paper
“ApoE4 hindering Aβ clearance significantly over ApoE3 and ApoE2 [14]”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [14]
In the citing paper
“In addition, the strongest genetic risk factor for LOAD, apolipoprotein E, APOE, in large part appears to increase risk via influencing Aβ seeding and clearance”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Castellano et al., 2011
In the citing paper
“Detailed in vivo microdialysis and stable isotope labeling kinetics experiments have demonstrated that ApoE regulates clearance of Aβ in the brain in an isoform-dependent manner (ApoE4-TR mice have diminished Aβ clearance relative to other TR mice), whereas Aβ production was not influenced by ApoE isoform”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Castellano et al., 2011
In the citing paper
“Compared with other ApoE isoforms, ApoE4 exacerbates the deposition of amyloid plaques in the brain98–100.”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [100]
In the citing paper
“This is further complicated by the fact that expression of different isoforms of human ApoE in transgenic mice results in different levels of plaque and CAA burden with apoE4 expression enhancing amyloid deposition compared to apoE3 or apoE2 [3, 21, 40, 59, 86, 178].”
From Alzheimer's disease: experimental models and reality (2017) · cites this paper as [21]
Citations
Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
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 · cited 2×
“Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian cells with amyloid peptide beta (1-40).”
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496 · cited 8×
“Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian cells with amyloid peptide beta (1-40).”
InfluentialAssociation of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786
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 · cited 1×
“For example, using in vivo stable isotopic labeling kinetics, our group recently reported that CSF Ab clearance and not synthesis is impaired in a small cohort of late-onset AD patients, although the effect of APOE genotype was not assessed (65).”
Self-citationCerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
Shaw, L. M., Vanderstichele, H., Knapik‐Czajka, M., Clark, C. M., Aisen, P. S., Petersen, R. C., Blennow, K., Soares, H., Simon, A., Lewczuk, P., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21610 · Cited by 2,065 · cited 3×
“Several groups have now validated molecular and neuroimaging biomarkers of the neuropathological hallmarks of AD (15-19).”
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920 · cited 2×
“Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian cells with amyloid peptide beta (1-40).”
The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · cited 5×
“Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian cells with amyloid peptide beta (1-40).”
InfluentialSelf-citationAmyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle
Kang, J.-E., Lim, M. M., Bateman, R. J., Lee, J. J., Smyth, L. P., Cirrito, J. R., Fujiki, N., Nishino, S., & Holtzman, D. M. (2009) · Science · doi:10.1126/science.1180962 · Cited by 1,565
Self-citationSchmechel, 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 · cited 3×
“allele, which markedly increases risk and reduces the age of onset (46), likely by accelerating the onset of brain Aβ accumulation (6-9).”
Cited by
Sorted by citations
Items 601–700 of 1,210
Light chain amyloidosis: Where are the light chains from and how they play their pathogenic role?
Zhang, C., Huang, X., & Li, J. (2017) · Blood Reviews · doi:10.1016/j.blre.2017.03.002 · Cited by 26
Cambronero, F. E., Liu, D., Neal, J. E., Moore, E. E., Gifford, K. A., Terry, J. G., Nair, S., Pechman, K. R., Osborn, K. E., Hohman, T. J., et al. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.02.009 · Cited by 25
“, 2016) and facilitates amyloid-beta (Aβ) accumulation (Castellano et al., 2011; Holtzman et al., 2000), which can induce endothelial damage and changes in vascular tone (Thomas et al.”
BackgroundHigh-density lipoprotein-related cholesterol metabolism in Alzheimer's disease
Pedrini, S., Chatterjee, P., Hone, E., & Martins, R. N. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15170 · Cited by 22
“SAA capacity to displace apolipoprotein from HDL is not limited to ApoA-I, since in the CSF SAA has been associated with the displacement of ApoE, the main brain-derived HDL apolipoprotein, with this effect being more prominent in ApoE4 individuals (Miida et al., 2006).”
BackgroundInfluentialThe Origins of Human Modernity
Bednarik, R. G. (2011) · Humanities · doi:10.3390/h1010001 · Cited by 25
“Their buildup is related to gene APOE versions e2, e3 and e4 [246].”
BackgroundAnimal Models of Alzheimer’s Disease
Newman, M., Kretzschmar, D., Khan, I., Chen, M., Verdile, G., & Lardelli, M. T. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809468-6.00040-1 · Cited by 25
He, K., Nie, L., Zhou, Q., Rahman, S. U., Liu, J., Yang, X., & Li, S. (2019) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00136 · Cited by 24
Endosomal Acid-Base Homeostasis in Neurodegenerative Diseases
Prasad, H., & Rao, R. (2020) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_2020_25 · Cited by 25
Alternative Targets to Fight Alzheimer’s Disease: Focus on Astrocytes
Valenza, M., Facchinetti, R., Menegoni, G., Steardo, L., & Scuderi, C. (2021) · Biomolecules · doi:10.3390/biom11040600 · Cited by 25
“A protein involved both in the clearance of Aβ and in its ability to aggregate and form fibrils is the apolipoprotein E (apoE) [68,69].”
BackgroundIslam, S., Sun, Y., Gao, Y., Nakamura, T., Noorani, A. A., Li, T., Wong, P. C., Kimura, N., Matsubara, E., Kasuga, K., et al. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.2039-21.2021 · Cited by 23
“For example, SAD patients carrying the ApoE4 allele show decreased A b clearance in the CSF compared with carriers of ApoE3 or ApoE2 allele ( Castellano et al., 2011; Yamazaki et al., 2019).”
Multifaceted Roles of Aquaporins in the Pathogenesis of Alzheimer’s Disease
Yamada, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076528 · Cited by 26
“isoform is the strongest genetic risk factor identified to date for developing late-onset AD, and it is associated with an increased accumulation of Aβ in the brain as well as tauassociated neurodegeneration [55,56].”
BackgroundLv, S., Zhang, Y., Lin, Y., Fang, W., Wang, Y., Li, Z., Lin, A., Dai, X., Ye, Q., Zhang, J., et al. (2023) · Aging Cell · doi:10.1111/acel.13932 · Cited by 24
Role of Syndecans in Lipid Metabolism and Human Diseases
Леонова, Е. И., & Galzitskaya, O. V. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-17344-3_10 · Cited by 26
Evaluating Circadian Dysfunction in Mouse Models of Alzheimer’s Disease: Where Do We Stand?
Sheehan, P. W., & Musiek, E. S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00703 · Cited by 23
Kim, H., Kim, S., Cho, B., Shin, J., & Kim, J. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00319-9 · Cited by 22
Self-citationWarfield, A. E., Gupta, P., Ruhmann, M. M., Jeffs, Q. L., Guidone, G. C., Rhymes, H. W., Thompson, M. I., & Todd, W. D. (2023) · Nature Communications · doi:10.1038/s41467-023-40546-w · Cited by 31
“Finally, the PLB1 model, which expresses APP, Tau, and PS1 only in the forebrain did not exhibit any circadian alterations 43 .”
The CETP I405V polymorphism is associated with an increased risk of Alzheimer’s disease
Yu, L., Shulman, J. M., Chibnik, L. B., Leurgans, S. E., Schneider, J. A., Jager, P. L. D., & Bennett, D. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00777.x · Cited by 24
“Importantly, recent evidence supports a role of APOE in regulating the clearance of amyloid beta peptide from the brain (Castellano et al., 2011), and it is possible that CETP also participates in this process.”
BackgroundA breach in the blood–brain barrier
Carmeliet, P., & Strooper, B. D. (2012) · Nature · doi:10.1038/485451a · Cited by 24
Neuroinflammation and Alzheimer's disease: Unravelling the molecular mechanisms
Kakkar, A., Singh, H., Singh, B. K., Kumar, A., Mishra, A. K., & Chopra, H. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251374353 · Cited by 26
“298,299 The deposited A β in the brains of aged patients with AD is thought to lead to the migration of microglia or other in fl ammatory cells to sites of A β deposit.”
Cognitive Impairment in Neurological Diseases: Lessons from Apolipoprotein E
Shi, J., Han, P., & Kuniyoshi, S. M. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130623 · Cited by 22
“A clearance in brain interstitial fluid microdialyzed from mice expressing human ApoE4 is significantly slower than those expressing ApoE2 or E3, but ApoE isoform does not affect amyloidogenic processing of A PP [25].”
BackgroundMolecular subtyping of Alzheimer’s disease with consensus non-negative matrix factorization
Zheng, C., & Xu, R. (2021) · PLoS ONE · doi:10.1371/journal.pone.0250278 · Cited by 21
“While some studies show APOE4 promotes AD by interaction with Aβ, especially it hinders Aβ clearance [52], other studies link APOE4 with synaptic function, such as synapse recycling [53].”
BackgroundVascular Dysfunction Is Central to Alzheimer’s Disease Pathogenesis in APOE e4 Carriers
McCorkindale, A. N., Mundell, H. D., Guennewig, B., & Sutherland, G. T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137106 · Cited by 23
“In the brain, APOE is primarily expressed in astrocytes, where it is the main lipid transporter, but it is also involved in cytoskeletal modulation [6], microglial modulation [7], and amyloid-beta clearance [8].”
BackgroundFarkas, S., Szabó, A., Török, B., Sólyomvári, C., Fazekas, C. L., Bánrévi, K., Correia, P., Chaves, T., & Zelena, D. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.985424 · Cited by 25
“However, in the locomotor activity represented by the number of entries to the dark compartment, a genotype effect was detected [F(1,30) = 9.”
BackgroundNa, H., Yang, J. B., Zhang, Z., Gan, Q., Tian, H., Rajab, I. M., Potempa, L. A., Tao, Q., & Qiu, W. Q. (2023) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2023.02.013 · Cited by 27
Hammond, T. C., Green, S. J., Jacobs, Y., Chlipala, G. E., Xing, X., Heil, S. D., Chen, A., Aware, C. B., Flemister, A., Stromberg, A. J., et al. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1227203 · Cited by 24
“Individuals with APOE ε4 alleles (APOE4) display altered brain function, such as reduced amyloid-beta clearance (Castellano et al., 2011) and increased inflammation (Shi et al.”
Bjerke, M., Kern, S., Blennow, K., Zetterberg, H., Wærn, M., Börjesson‐Hanson, A., Östling, S., Kern, J., & Skoog, I. G. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150525 · Cited by 22
“The E4 variant of APOE seems to be related to A dysmetabolism and/or aggregation [5, 6].”
BackgroundGrimmer, T., Goldhardt, O., Guo, L., Yousefi, B. H., Förster, S., Drzezga, A. E., Sorg, C., Alexopoulos, P., Förstl, H., Kurz, A., et al. (2014) · NeuroImage Clinical · doi:10.1016/j.nicl.2014.01.016 · Cited by 23
“ApoE and LRP-1 are both involved in clearance pathways for β-amyloid (Castellano et al., 2011).”
BackgroundResultEffects of glucose and insulin on secretion of amyloid‐β by human adipose tissue cells
Tharp, W. G., Gupta, D., Smith, J. S., Jones, K. P., Jones, A. M., & Pratley, R. E. (2016) · Obesity · doi:10.1002/oby.21494 · Cited by 25
“Ab recovery was calibrated by dialyzing plasma in vitro (n 5 8; Figure 3a) (27).”
BackgroundMethodGenetic discoveries and advances in late‐onset Alzheimer’s disease
Rezazadeh, M., Hosseinzadeh, H., Moradi, M., Esfahani, B. S., Talebian, S., Parvin, S., & Gharesouran, J. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28372 · Cited by 23
“The rs9331888 and rs11136000 SNPs are associated with plasma CLU levels, whereas rs9331888 polymorphism is also correlated with expression of an alternative splice variant (Castellano et al., 2011; Y.‐Y. Xing et al., 2012).”
BackgroundApolipoprotein E in Alzheimer’s Disease: Focus on Synaptic Function and Therapeutic Strategy
Qu, L., Xu, S., Lan, Z., Fang, S., Xu, Y., & Zhu, X. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04449-1 · Cited by 22
Budny, V., Ruminot, I., Wybitul, M., Treyer, V., Barros, L. F., & Tackenberg, C. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03550-w · Cited by 25
“While the APOE effect on several AD-related pathologies, such as A β generation and clearance [28, 29] or tau-induced neurodegeneration, neuroin fl ammation and BBB disruption [30], has already been extensively studied (for details see [31, 32]), the knowledge on the role of different APOE isoforms…”
Apolipoprotein E Interferes with IAPP Aggregation and Protects Pericytes from IAPP-Induced Toxicity
Gharibyan, A. L., Islam, T., Pettersson, N., Surano, S., Lundgren, J., Johansson, G., Genot, M., Schultz, N., Wennström, M., & Olofsson, A. (2020) · Biomolecules · doi:10.3390/biom10010134 · Cited by 22
“In contrast, several works have suggested that ApoE plays an important role in the degradation and clearance of Aβ amyloid [15,17,33,34].”
BackgroundThe effect of ApoE ε 4 on clinical and structural MRI markers in prodromal Alzheimer’s disease
Initiative, A. D. N., Zhang, C., Kong, M., Wei, H., Zhang, H., Ma, G., & Ba, M. (2020) · Quantitative Imaging in Medicine and Surgery · doi:10.21037/qims.2020.01.14 · Cited by 21
“ApoE ε 4-associated cerebral Aβ deposition might be illustrated by the ApoE ε 4 allele being associated with enhanced Aβ deposition into plaques and the differentially regulated clearance of Aβ from the brain (43-46).”
BackgroundOjo, J. O., Reed, J. M., Crynen, G. C., Vallabhaneni, P., Evans, J., Shackleton, B., Eisenbaum, M., Ringland, C., Edsell, A., MULLAN, M. J., et al. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.658605 · Cited by 22
“role in regulating the metabolism and perivascular drainage of Aβ and other soluble metabolites in extracellular fluids of the brain (Kim et al., 2009; Castellano et al., 2011; Cramer et al., 2012; Verghese et al., 2013; Kanekiyo et al., 2014).”
BackgroundAPOEε4 and risk of Alzheimer’s disease – time to move forward
Lefterov, I. M., Fitz, N. F., Lü, Y., & Koldamova, R. P. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1195724 · Cited by 25
“In APP transgenic mice expressing human APOE isoforms, APOE affects Aβ clearance and deposition in an isoform-dependent manner (Holtzman et al., 2000; Bales et al., 2009; Castellano et al., 2011; Kim et al., 2011), and APOE lipidation level is of significance (Fitz et al.”
BackgroundFaraji, P., Kühn, H., & Ahmadian, S. (2024) · Journal of Molecular Neuroscience · doi:10.1007/s12031-024-02224-4 · Cited by 25
“Although the efflux mechanisms have not been studied in detail, several proteins including APOE isoforms have been implicated in the clearing process (Castellano et al. 2011).”
BackgroundYe, Q., Su, F., Shu, H., Gong, L., Xie, C., Zhang, Z., & Bai, F. (2016) · Brain Imaging and Behavior · doi:10.1007/s11682-016-9623-5 · Cited by 23
“The ε4 allele could increase the Aβ load and reduce the Aβ clearance, thus accelerating brain Aβ deposition in ε4 carriers (Castellano et al. 2011; Morris et al. 2010; Reiman et al. 2009).”
BackgroundCamargo, L. C., Campos, G. A. A., Galante, P., Biolchi, A. M., Gonçalves, J. C., Lopes, K. S., & Mortari, M. R. (2017) · Neuropeptides · doi:10.1016/j.npep.2017.11.010 · Cited by 21
Zhang, A., Zhao, Q., Xu, D., & Jiang, S. (2018) · Scientific Reports · doi:10.1038/s41598-018-26398-1 · Cited by 20
Chen, X. R., Initiative, A. D. N., Shao, Y., & Sadowski, M. J. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210434 · Cited by 22
“clearance of soluble A peptides from the brain 63 [8] and more effectively catalyzes assembly of A 64 peptides into oligomeric and fibrillar aggregates [9, 65 10], eventually promoting A deposition and toxi66 city disproportionally to other isoforms.”
BackgroundWang, J., Ohno‐Matsui, K., & Morita, I. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.07.014 · Cited by 21
Liao, F., Zhang, T. J., Mahan, T. E., Jiang, H., & Holtzman, D. M. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.09.005 · Cited by 21
“ISF Aβ was measured with a sandwich ELISA using anti-Aβ13-28 m266 (a gift from Eli Lilly and Company) as the coating antibody and anti-Aβ1-5 3D6-biotin (a gift from Eli Lilly and Company) as the detecting antibody (Castellano et al., 2011).”
MethodSelf-citationLysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction
Krogsaeter, E., McKetney, J., Valiente‐Banuet, L., Marquez, A., Willis, A., Cakir, Z., Stevenson, E. J., Jang, G. Μ., Rao, A. T., Li, E., et al. (2025) · Autophagy · doi:10.1080/15548627.2025.2576613 · Cited by 22
“At a cellular level, APOE4 interferes with cytoskeletal and microtubule structure [28–31], β-amyloid clearance [32– 34], tau dynamics [11], metabolism [35–37], and endolysoso-mal function [15,26,38–41].”
Apolipoprotein E, cognitive function, and cognitive decline among older Taiwanese adults
Todd, M. A., Schneper, L. M., Vasunilashorn, S. M., Notterman, D. A., Ullman, M. T., & Goldman, N. (2018) · PLoS ONE · doi:10.1371/journal.pone.0206118 · Cited by 22
Rosa, F. L., Agostini, S., Bianchi, A., Nemni, R., Piancone, F., Marventano, I., Mancuso, R., Saresella, M., & Clerici, M. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-019-2034-9 · Cited by 21
Astrocytes in Neurodegenerative Diseases: A Perspective from Tauopathy and α-Synucleinopathy
Wang, P., & Ye, Y. (2021) · Life · doi:10.3390/life11090938 · Cited by 21
Ghosh, I., Liu, C. S., Swardfager, W., Lanctôt, K. L., & Anderson, N. D. (2021) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2021.103683 · Cited by 20
Patients with Alzheimer’s disease have an increased removal rate of soluble beta-amyloid-42
Zaretsky, D. V., Zaretskaia, M. V., Molkov, Y. I., & Initiative, A. D. N. (2022) · PLoS ONE · doi:10.1371/journal.pone.0276933 · Cited by 25
Stroh, M. A., Swerdlow, R. H., & Zhu, H. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.11.022 · Cited by 20
Botanics: a potential source of new therapies for Alzheimer's disease?
Devi, P., & Syad, A. N. (2014) · Botanics Targets and Therapy · doi:10.2147/btat.s33554 · Cited by 24
“It has long been known that apolipoprotein E (APOE4) is involved in the binding and metabolism of lipids, and in the clearance of Aβ from the brain.(27) A protein variant APOE4 of mice induces a destructive inflammatory response in pericytes (cells that wrap around blood vessels and seal off the BBB).”
Future horizons in Alzheimer's disease research
Wısnıewskı, T., & Drummond, E. (2019) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2019.08.001 · Cited by 20
Apolipoprotein E Facilitates Amyloid-β Oligomer-Induced Tau Phosphorylation
Hou, T.-T., Han, Y.-D., Cong, L., Liu, C.-C., Liang, X.-Y., Xue, F.-Z., & Du, Y.-F. (2020) · Journal of Alzheimer’s Disease · doi:10.3233/jad-190711 · Cited by 20
Ghaffari, M. S., Sanadgol, N., & Abdollahi, M. R. (2020) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557520666200513122357 · Cited by 20
Guyon, A., Rousseau, J., Lamothe, G., & Tremblay, J. P. (2020) · PLoS ONE · doi:10.1371/journal.pone.0237122 · Cited by 20
“A673T might also compensate for a weak clearing system which has been associated with sporadic AD cases by changing the conformation of the Aβ peptides [37].”
BackgroundWhat does it mean to be ‘amyloid-positive’?
Fagan, A. M. (2015) · Brain · doi:10.1093/brain/awu387 · Cited by 22
Self-citationZhang, L., Xu, J., Gao, J., Chen, P., Yin, M., & Zhao, W. (2019) · Immunity & Ageing · doi:10.1186/s12979-018-0142-7 · Cited by 20
“Especially, they differentially affect the clearance of brain Aβ into glia or into the periphery, and APOE4 has much lower efficiency in Aβ clearance in mouse models that express human APOE gene [7, 8].”
BackgroundZhang, Q., Song, Q., Gu, X., Zheng, M., Wang, A., Jiang, G., Huang, M., Chen, H., Qiu, Y., Bo, B., et al. (2021) · Advanced Science · doi:10.1002/advs.202001918 · Cited by 19
Using Drosophila amyloid toxicity models to study Alzheimer's disease
Tsintzas, E., & Niccoli, T. (2024) · Annals of Human Genetics · doi:10.1111/ahg.12554 · Cited by 20
“Sporadic inheritance of the ε 4 isoform of apolipoprotein E (APOE) is considered the most prominent genetic risk factor of LOAD (Bekris et al., 2010) and has been demonstrated to increase amyloid burden in the brains of AD patients (Castellano et al., 2011).”
InfluentialCurrent insights into apolipoprotein E and the immune response in Alzheimer's disease
Lin, P. B., & Holtzman, D. M. (2024) · Immunological Reviews · doi:10.1111/imr.13414 · Cited by 19
Self-citationMurphy, K. B., Hu, D., Wolfs, L., Rohde, S. K., Fauró, G. L., Geric, I., Mancuso, R., De Strooper, B., & Marzi, S. J. (2025) · Nature Communications · doi:10.1038/s41467-025-60099-4 · Cited by 25
“…accumulation of myelin debris in APOE2 -TR mice 51 , and increased clearanceofA β fromtheinterstitial fl uidofmiceexpressingtheAPOE2 isoform 50 In addition, APOE2 -expressing macrophages derived from transgenic mice with an APP mutation were also more ef fi cient at degrading amyloid beta…”
O'Callaghan, P. W., Noborn, F., Sehlin, D., Li, J., Lannfelt, L., Lindahl, U., & Zhang, X. (2014) · Amyloid · doi:10.3109/13506129.2013.879643 · Cited by 20
“apolipoprotein E (ApoE)-isoform-dependent manner [2].”
BackgroundClusterin as a Potential Biomarker of Obesity-Related Alzheimer’s Disease Risk
Bradley, D. P. (2020) · Biomarker Insights · doi:10.1177/1177271920964108 · Cited by 20
Pedrini, S., Doecke, J. D., Hone, E., Wang, P., Thota, R. N., Bush, A. I., Rowe, C. C., Doré, V., Villemagne, V. L., Ames, D. J., et al. (2022) · Journal of Neurochemistry · doi:10.1111/jnc.15681 · Cited by 20
“…oligomerization (Bales et al., 2009; Hashimoto et al., 2012; Koffie et al., 2012; Ye et al., 2005; Youmans et al., 2012) and with reduced Aβ clearance (Castellano et al., 2011; report, we have assessed the HDL- cargo (Cholesterol, ApoA- I, ApoA- II, ApoC- I, ApoCIII, ApoD, ApoE, ApoH, ApoJ, CRP,…”
Evidence that Alzheimer’s Disease Is a Disease of Competitive Synaptic Plasticity Gone Awry
Huang, Z. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-240042 · Cited by 20
Potential Therapeutic Implications of Gelsolin in Alzheimer's Disease
Ji, L., Zhao, X., & Hua, Z. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-141548 · Cited by 20
Roeben, B., the TREND study team, Maetzler, W., Vanmechelen, E., Schulte, C., Heinzel, S., Stellos, K., Godau, J., Huber, H., Brockmann, K., et al. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-150575 · Cited by 19
“4 allele is known as a genetic risk factor for both AD and cardiovascular disease (CVD) [22–24].”
Is ApoE ɛ 4 a good biomarker for amyloid pathology in late onset Alzheimer’s disease?
Ba, M., Kong, M., Li, X., Ng, K. P., Rosa‐Neto, P., & Gauthier, S. G. (2016) · Translational Neurodegeneration · doi:10.1186/s40035-016-0067-z · Cited by 20
High-Throughput Mass Spectrometry Assay for Quantifying β-Amyloid 40 and 42 in Cerebrospinal Fluid
Weber, D. M., Tran, D., Goldman, S. M., Taylor, S. W., Ginns, E. I., LAGIER, R. J., Rissman, R. A., Brewer, J. B., & Clarke, N. J. (2019) · Clinical Chemistry · doi:10.1373/clinchem.2018.300947 · Cited by 19
The Rationale for Insulin Therapy in Alzheimer’s Disease
Ribarič, S. (2016) · Molecules · doi:10.3390/molecules21060689 · Cited by 20
Cholesterol Metabolism in CNS Diseases: The Potential of SREBP2 and LXR as Therapeutic Targets
Wang, N.-Q., Sun, P.-X., Shen, Q.-Q., & Deng, M.-Y. (2025) · Molecular Neurobiology · doi:10.1007/s12035-024-04672-w · Cited by 19
“Furthermore, a recent in vivo study has demonstrated that the clearance of soluble Aβ from CSF is dependent on the expression of human APOE isoforms (APOE4 APOE3 ≤ APOE2) [95].”
Golden, L. R., Siano, D. S., Stephens, I. O., MacLean, S. M., Saito, K., Nolt, G. L., Funnell, J. L., Pallerla, A. V., Lee, S., Smith, C., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-02094-y · Cited by 18
“Additionally, microglia cluster around Aβ deposits in CAA 49 .”
InfluentialHu, H., Wan, S., Hu, Y., Wang, Q., Li, H., & Zhang, N. (2025) · Annals of Medicine · doi:10.1080/07853890.2024.2445194 · Cited by 20
“…impact Aβ aggregation according to an analysis of cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers in a cohort of cognitively normal individuals, and APOE4 promotes the formation of Aβ protofibrils more effectively than APOE2 and APOE3 in a β-amyloidosis mouse model [28].”
Lampert, E. J., Choudhury, K. R., Hostage, C. A., Petrella, J. R., Doraiswamy, P. M., & Initiative, T. A. D. N. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060747 · Cited by 20
“Prior autopsy, CSF and PET studies have linked ApoE4 to an amyloid phenotype and hippocampal changes [6–10] [26], and studies have documented ApoE4 effects on greater neocortical amyloid-beta deposition and/or reduced clearance [6] [27].”
Régy, M., Dugravot, A., Sabia, S., Fayossé, A., Mangin, J., Marie Chupin, A., Fischer, C., Bouteloup, V., Dufouil, C., Chêne, G., et al. (2022) · NeuroImage · doi:10.1016/j.neuroimage.2022.118966 · Cited by 23
A meta-analysis of the relationship between sleep and β-Amyloid biomarkers in Alzheimer’s disease
Harenbrock, J., Holling, H., Reid, G., & Koychev, I. G. (2023) · Biomarkers in Neuropsychiatry · doi:10.1016/j.bionps.2023.100068 · Cited by 20
The molecular spectrum of amyloid‐beta (Aβ) in neurodegenerative diseases beyond Alzheimer's disease
Ichimata, S., Yoshida, K., Li, J., Rogaeva, E. A., Lang, A. E., & Kovács, G. G. (2023) · Brain Pathology · doi:10.1111/bpa.13210 · Cited by 17
“As the apoE4 protein is less efficient at clearing A β [74], the abnormal accumulation of A β protein is considered one of the main causes of increased risk for AD [75].”
BackgroundYadav, V., Mythri, C., & Kumarasamy, M. (2024) · Brain Behavior and Immunity Integrative · doi:10.1016/j.bbii.2024.100048 · Cited by 22
Mitani, Y., Yarimizu, J., Akashiba, H., Shitaka, Y., Ni, K., & Matsuoka, N. (2012) · Journal of Neurochemistry · doi:10.1111/jnc.12125 · Cited by 18
Segev, Y., Livne, A., Mints, M., & Rosenblum, K. (2016) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2016.00170 · Cited by 18
“…of the beta-amyloid (Aβ) peptide, lipid and cholesterol metabolism, inflammation, mitochondrial dysfunction, neuronal function, and to a lesser extent, amyloid precursor protein (APP) cleavage (Mahley and Rall, 2000; He et al., 2007; Castellano et al., 2011; Chen et al., 2012; Dafnis et al., 2012).”
BackgroundCerebrospinal Fluid Proteins as Regulators of Beta‐amyloid Aggregation and Toxicity
Pate, K. M., & Murphy, R. M. (2017) · Israel Journal of Chemistry · doi:10.1002/ijch.201600078 · Cited by 17
Joo, S. H., Hahn, C., Lim, H. K., Yoon, K. D., Yoon, S. H., & Lee, C. U. (2019) · Psychiatry Investigation · doi:10.30773/pi.2019.06.17 · Cited by 19
Geerts, H., & Spiros, Ä. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12082 · Cited by 19
Gotoh, N., Saito, Y., Hata, S., Saito, H., Ojima, D., Murayama, C., Shigeta, M., Abe, T., Konno, D., Matsuzaki, F., et al. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.012386 · Cited by 18
Zinc affects the proteolytic stability of Apolipoprotein E in an isoform-dependent way
Xu, H. J., Gupta, V. B., Martins, I. J., Martins, R. N., Fowler, C. J., Bush, A. I., Finkelstein, D. I., & Adlard, P. A. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.06.016 · Cited by 20
Ramos de Matos, M., Ferreira, C., Herukka, S.-K., Soininen, H., Janeiro, A., Santana, I., Baldeiras, I., Almeida, M. R., Lleó, A., Dols-Icardo, O., et al. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-180512 · Cited by 18
Femminella, G. D., Initiative, T. A. D. N., Taylor‐Davies, G., Scott, J., & Edison, P. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180365 · Cited by 20
“have higher amyloid burden than non-carriers [23].”
Fatigue in Alzheimer’s disease: biological basis and clinical management—a narrative review
Angioni, D., Raffin, J., Ousset, P., Delrieu, J., & Barreto, P. D. S. (2023) · Aging Clinical and Experimental Research · doi:10.1007/s40520-023-02482-z · Cited by 20
“1 3 Brain Aβ pathology is associated with the apolipoprotein E (Apo-ε) gene polymorphism, it is known that the Apo-ε4 allele decreases Aβ clearance [17].”
BackgroundMcFall, G. P., Sapkota, S., McDermott, K. L., & Dixon, R. A. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.02.032 · Cited by 17
“The isoforms differentially regulate amyloid beta (Ab) aggregation and clearance, glucose metabolism, neuroinflammation, lipid transport, mitochondrial function, and neuronal signaling (Bennet et al., 2007; Castellano et al., 2011; Corder et al., 1993; Liu et al., 2013).”
Slot, R. E. R., Kester, M. I., van Harten, A. C., Jongbloed, W., Bouwman, F. H., Teunissen, C. E., Scheltens, P., van der Flier, W. M., & Veerhuis, R. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.02.017 · Cited by 18
Physiological and Pathological Functions of Beta-Amyloid in the Brain and Alzheimer'S Disease
Volicer, L. (2020) · The Chinese Journal of Physiology · doi:10.4103/cjp.cjp_10_20 · Cited by 18
Defective Lysosomal Lipid Catabolism as a Common Pathogenic Mechanism for Dementia
Lee, J. Y., Marian, O. C., & Don, A. S. (2021) · NeuroMolecular Medicine · doi:10.1007/s12017-021-08644-4 · Cited by 18
Study of Exosomes Shed New Light on Physiology of Amyloidogenesis
van Niel, G. (2016) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-016-0357-0 · Cited by 20
Traversy, M.-T., Vandal, M., Tremblay, C., Tournissac, M., Giguère-Rancourt, A., Bennett, A. D., & Calon, F. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.11.028 · Cited by 16
Bumber, J. R., Rački, V., Mežnarić, S., Pelčić, G., & Mršić‐Pelčić, J. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14176047 · Cited by 19
“…PET imaging studies have demonstrated that, among cognitively normal individuals, A β deposition is the highest in those with the APOE4/E4 genotype, with the pattern of amyloid accumulation consistently following the order: APOE4/E > APOE4/E3 > APOE3/E3 > APOE2/E3 across all age groups [175,176].”
Shanks, H. R. C., Onuska, K. M., Barupal, D. K., Schmitz, T. W., & Initiative, A. D. N. (2022) · Brain Communications · doi:10.1093/braincomms/fcac318 · Cited by 17
Lou, T.-W., Tao, B., & Chen, M. (2023) · Neuroscience · doi:10.1016/j.neuroscience.2023.01.032 · Cited by 17
Mitochondria Profoundly Influence Apolipoprotein E Biology
Gabrielli, A. P., Weidling, I. W., Ranjan, A., Wang, X., Novikova, L., Chowdhury, S. R., Menta, B. W., Berkowicz, A., Wilkins, H., Peterson, K. R., et al. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-221177 · Cited by 16
Rajendra, A., Bondonno, N. P., Murray, K., Zhong, L., Rainey‐Smith, S. R., Gardener, S. L., Blekkenhorst, L. C., Ames, D. J., Maruff, P. T., Martins, R. N., et al. (2023) · Clinical Nutrition · doi:10.1016/j.clnu.2023.05.022 · Cited by 17
Eisenbaum, M., Pearson, A., Ortiz, C., Koprivica, M., Cembran, A., MULLAN, M. J., Crawford, F., Ojo, J. O., & Bachmeier, C. J. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.114702 · Cited by 18
Mansuy, M., Baille, S., Canet, G., Borie, A. M., Cohen‐Solal, C., Vignes, M., Perrier, V., Chevallier, N., Guern, N. L., Deckert, V., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.24802 · Cited by 16
“Although several mechanisms for the effect of the apoE4 variant on AD pathogenesis have been proposed, the primary pathway appears to be the differential effects of apoE isoforms on Aβ aggregation and clearance [60, 61].”
BackgroundEffects of apolipoprotein E on nutritional metabolism in dementia
Farmer, B. C., Johnson, L. A., & Hanson, A. J. (2018) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000566 · Cited by 16
Metadata
- Authors
- Castellano, J. M., Kim, J., Stewart, F. R., Jiang, H., DeMattos, R. B., Patterson, B. W., Fagan, A. M., Morris, J. C., Mawuenyega, K. G., Cruchaga, C., Goate, A. M., Bales, K. R., Paul, S. M., Bateman, R. J., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Eli Lilly (United States) (US)
- Pfizer (United States) (US)
- Cornell University (US)
- Corresponding author
- Castellano, Joseph M.
- Kim, Jungsu
- Holtzman, David M.
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2011-06-29
- Volume
- 3
- Issue
- 89
- Pages
- 89ra57-89ra57
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC3192364
- OpenAlex
- W2112499304
- Cited by
- 1,242
- References
- 67
- Citations by year
- 2026: 64 · 2025: 74 · 2024: 89 · 2023: 95 · 2022: 77 · 2021: 82 · 2020: 107 · 2019: 90 · 2018: 74 · 2017: 88 · 2016: 91 · 2015: 64 · 2014: 81 · 2013: 73 · 2012: 71
- FWCI
- 28.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p30ns069329-02)
- National Institute on Aging (R01AG013956, F31AG034004, P50AG005681, P01AG003991, R37AG013956, AG13956, K23AG030946, P01AG026276)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK056341)
- National Institute of Neurological Disorders and Stroke (P30-NS069329, NS034467, R37NS034467, P30NS057105, P30 NS069329-01, R01NS034467)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein E isoforms, APOE ε4, APOE ε2, amyloid-beta clearance, amyloid-beta deposition, Alzheimer's disease risk, brain interstitial fluid, APP processing, amyloid plaques, neuroimaging biomarkers, cognitively normal older adults
- MeSH terms
- Adult, Aged, Alleles, Alzheimer Disease, Animals, Brain, Female, Genotype, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Biomarkers, Amyloid beta-Peptides, Microdialysis, Protein Isoforms, Mice, Apolipoprotein E4
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