The DOI matches its Crossref record; 180 of the 180 references it cites were found in a registry or an index.
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Open accessAbstract
Apolipoprotein E (Apo-E) is a major cholesterol carrier that supports lipid transport and injury repair in the brain. APOE polymorphic alleles are the main genetic determinants of Alzheimer disease (AD) risk: individuals carrying the ε4 allele are at increased risk of AD compared with those carrying the more common ε3 allele, whereas the ε2 allele decreases risk. Presence of the APOE ε4 allele is also associated with increased risk of cerebral amyloid angiopathy and age-related cognitive decline during normal ageing. Apo-E-lipoproteins bind to several cell-surface receptors to deliver lipids, and also to hydrophobic amyloid-β (Aβ) peptide, which is thought to initiate toxic events that lead to synaptic dysfunction and neurodegeneration in AD. Apo-E isoforms differentially regulate Aβ aggregation and clearance in the brain, and have distinct functions in regulating brain lipid transport, glucose metabolism, neuronal signalling, neuroinflammation, and mitochondrial function. In this Review, we describe current knowledge on Apo-E in the CNS, with a particular emphasis on the clinical and pathological features associated with carriers of different Apo-E isoforms. We also discuss Aβ-dependent and Aβ-independent mechanisms that link Apo-E4 status with AD risk, and consider how to design effective strategies for AD therapy by targeting Apo-E.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“and equivalent expression of E2 almost cancels out the deleterious effect of the E4 allele.6,14,15”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [15]
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
“E2/E4 heterozygotes have only double the risk of E3/E3 homozygotes”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [15]
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
“Epidemiological evidence and evidence from neuropathological assessment of the impact of apoE isoforms on the brain Aβ load, have suggested that apoE2 exerts a protective effect against Aβ pathology and AD morbidity [3,9,10], while apoE4, in contrast, markedly enhances the disease process [7,8,30].”
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 [3]
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
“A single copy of the APOE ε4 allele endows a ~3 fold increase in AD risk, and 2 APOE ε4 copies result in a ~15 fold risk increase, while an APOE ε2 allele halves AD risk relative to 2 copies of ε3 (reviewed in [4]).”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [4]
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
“A single copy of the APOE ε4 allele endows a ~3 fold increase in AD risk, and 2 APOE ε4 copies result in a ~15 fold risk increase, while an APOE ε2 allele halves AD risk relative to 2 copies of ε3 (reviewed in [4]).”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [4]
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
“Recently, we identified functional siRNA sequences targeting Apolipoprotein E (ApoE), implicated in several neurodegenerative diseases, including Alzheimer’s disease and Amyotrophic Lateral Sclerosis26–28 (Ferguson et al., manuscript in preparation).”
From A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system (2019) · cites this paper as [26]
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
“Established risk factors for AD include advanced age > 65 years, female sex, and most importantly, the Apolipoprotein E (ApoE) ε4 allele [20,23].”
From Clonal Hematopoiesis of Indeterminate Potential as an Emerging Interdisciplinary Risk Factor in Alzheimer’s Disease: Current Evidence and Future Directions (2026) · cites this paper as [23]
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 ApoE ε4 eleveates risk of AD by about three–four-fold, ApoE ε2 is associated with a protective effect, and ApoE ε3, as the most prevalent isoform in the general population, is considered largely neutral [23].”
From Clonal Hematopoiesis of Indeterminate Potential as an Emerging Interdisciplinary Risk Factor in Alzheimer’s Disease: Current Evidence and Future Directions (2026) · cites this paper as [23]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In addition, several studies have demonstrated that increasing apoE lipidation, either through genetic or pharmacological approaches, promotes Aβ clearance and improves cognitive performance in mice (27, 44, 45).”
From APOE3 -Jacksonville (V236E) variant reduces self-aggregation and risk of dementia (2021) · cites this paper as [27]
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 the central nervous system, neurons are the primary source of extracellular Aβ, which is generated through amyloidogenic processing of amyloid precursor protein (APP), while non-neuronal cells, particularly astrocytes, play important roles in Aβ uptake and clearance from the extracellular space (Liu et al., 2013).”
From Isogenic human stem cell models reveal mutation-dependent protective mechanisms of APOE3 Christchurch (2026) · cites this paper as Liu et al., 2013
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
“Besides AD43, APOE has been associated with at least eighteen other diseases, including heart disease and high cholesterol44.”
From Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease (2024) · cites this paper as [43]
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 contrast, ApoE4 exists in 20% of the population; however it comprises nearly 65% of AD cases (Kim et al., 2009;Liu et al., 2013).”
From Human ApoE Isoforms Differentially Modulate Brain Glucose and Ketone Body Metabolism: Implications for Alzheimer's Disease Risk Reduction and Early Intervention (2018) · cites this paper as Liu et al., 2013
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
“Each ApoE4 allele increases AD risk by 3- to 4-fold while lowering the age at onset by ~8 years (Liu et al., 2013).”
From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Liu et al., 2013
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
“The apolipoprotein E4 (APOE4) allele is the most common and important genetic risk factor for late-onset sporadic AD [19–21].”
From 25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner (2020) · cites this paper as [20]
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
“Interestingly, CE production is overactive in human SAD fibroblasts (Pani et al., 2009) and APOE, the major genetic risk factor for SAD, acts as a CE transporter in brain (Liu et al., 2013, Michikawa et al., 2000, Minagawa et al., 2009).”
From Cholesterol Metabolism Is a Druggable Axis that Independently Regulates Tau and Amyloid-β in iPSC-Derived Alzheimer’s Disease Neurons (2019) · cites this paper as Liu et al., 2013
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
“Neurons appear incapable of increasing cholesterol synthesis to compensate for astrocyte deficiency in any appreciable way (48).”
From Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol (2021) · cites this paper as [48]
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
“Due to the apoE4 allele being the greatest risk factor associated with development of AD”
From The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor Complex Are Responsible for the Cellular Uptake of Aβ42 and Its Protein Aggregates (2020) · cites this paper as [42]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Apolipoprotein E4 ( APOE4 ) is the major genetic risk factor for sporadic AD (258, 368, 612, 681).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [368]
The cited source says what the claim attributes to it.
In the citing paper
“There is strong experimental evidence that the APOE isoforms are major determinants of the amount and quality of amyloid-β peptide (Aβ) and amyloid burden in the brain that develops during aging.15–17”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“Previous human and animal studies have already established the baseline consequences of APOE3 and APOE4 in the absence of amyloid pathology. 60 , 61 , 62 , 63”
From Apolipoprotein ε4 exacerbates white matter impairment in a mouse model of Aβ amyloidosis by decreasing actively myelinating oligodendrocytes (2025) · cites this paper as [62]
The cited source says what the claim attributes to it.
In the citing paper
“APOE4 is the major genetic risk factor for sporadic, late-onset AD (199, 368, 580, 612).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [368]
The cited source says what the claim attributes to it.
In the citing paper
“For these cases, the strongest genetic risk factor is the apolipoprotein E (ΑPOE) ε4 allele. 2 , 3”
From Deletion of miR-33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice (2024) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“ApoE is also a crucial factor in the development of AD (5, 6, 31, 32).”
From The E3 ubiquitin ligase Idol controls brain LDL receptor expression, ApoE clearance, and Aβ amyloidosis (2015) · cites this paper as [32]
The cited source says what the claim attributes to it.
In the citing paper
“In the far more prevalent sporadic AD, the mechanism(s) underlying disturbance of Aβ homeostasis are less obvious, but inheritance of the apolipoprotein (apo) E isoforms has been thus far established by numerous independent studies as the strongest genetic factor modulating overall risk of occurrence of the disease and age of onset (reviewed in [3]).”
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 [3]
The cited source says what the claim attributes to it.
In the citing paper
“To provide a mechanistic explanation for the variable effect of apoE isoforms on Aβ accumulation and overall disease risk, it has been proposed that they produce a differential effect on Aβ clearance and Aβ aggregation and deposition [3].”
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 [3]
The cited source says what the claim attributes to it.
In the citing paper
“A single copy of the APOE ε4 allele endows a ~3 fold increase in AD risk, and 2 APOE ε4 copies result in a ~15 fold risk increase, while an APOE ε2 allele halves AD risk relative to 2 copies of ε3 (reviewed in [4]).”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“Susceptibility to sporadic AD is foremost modulated by APOE genotype, which also influences the load of Aβ parenchymal plaques and vascular Aβ (VAβ) deposits.”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“ApoE has been shown to independently influence several key factors that drive pathogenesis of AD, including 𝛃 -amyloidosis, tauopathy, and synaptic dysfunction (1-3).”
From Therapeutic Idol reduction ameliorates amyloidosis and improves cognitive function in APP/PS1 mice (2020) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“As stated, APOE4 is the strongest genetic risk factor for late-onset AD (5, 27).”
From APOE3 -Jacksonville (V236E) variant reduces self-aggregation and risk of dementia (2021) · cites this paper as [27]
The cited source says what the claim attributes to it.
In the citing paper
“The three isoforms differ at two residues: ApoE2 carries Cys112/Cys158, ApoE3 carries Cys112/Arg158, and ApoE4 carries Arg112/Arg158.”
The cited source says what the claim attributes to it.
In the citing paper
“APOE mainly exists in three allelic variants, APOE2, E3, and E4, which differ in a single amino acid change at position 112 or 158: APOE2 (Cys112, Cys158), APOE3 (Cys112, Arg158), and APOE4 (Arg112, Arg158) (Liu et al., 2013).”
From APOE2, E3, and E4 differentially modulate cellular homeostasis, cholesterol metabolism, and inflammatory response in isogenic iPSC-derived astrocytes (2022) · cites this paper as Liu et al., 2013
The cited source says what the claim attributes to it.
In the citing paper
“The ε4 allele is the strongest common genetic risk factor for sporadic AD”
From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“influencing disease risk, age at onset, and multiple aspects of the biological phenotype in a dose-dependent manner [6, 7].”
From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“the ε4 isoform (ApoE4) is the strongest genetic risk factor for the predominant, late-onset form of Alzheimer’s disease (AD).”
From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Liu et al., 2013
The cited source says what the claim attributes to it.
In the citing paper
“ApoE4 increases risk for AD”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“lowers the age of onset [4–14]”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“ApoE4 was also suggested to be less efficient than ApoE3 in transporting brain cholesterol [33]”
From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [33]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In humans, the APOE4 and APOE2 alleles are codominant”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [15]
Experimental — accuracy not yet measuredIn the citing paper
“Conversely, ApoE2 is considered to be protective against AD, while ApoE3 is considered risk-neutral”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [13]
In the citing paper
“The allele frequency of ApoE4 is 15–20%, with some variation in incidence between populations [13].”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [13]
In the citing paper
“Compelling evidence demonstrates that the ε4 allele is potently associated with late AD onset [318, 443, 451].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [451]
In the citing paper
“Hence, APOEε4, which has been implicated in AD pathophysiology and pathogenesis by processes mainly linked to Aβ but also associated with Aβ-independent pathways [15], may be the missing link connecting Aβ to tau via actions of αSyn.”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [15]
In the citing paper
“The apoE3 and apoE4 amino acid sequences differ only at position 112 where apoE4 has an Arg instead of a Cys.”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [6]
In the citing paper
“Apolipoprotein (apo) E4, an isoform of the APOE gene in humans, is the major genetic risk factor for late-onset familial and sporadic AD [4–8], which account for most AD cases.”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [6]
In the citing paper
“Both of these pathologies are exacerbated by the presence of apoE4 [4–7, 12].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [6]
In the citing paper
“ApoE4 increases the risk and decreases the age of onset of AD in a gene dose dependent manner [4–11].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [6]
In the citing paper
“Overall, it has been demonstrated, both in vivo and in vitro, that apoE plays major roles in AD pathogenesis in both an Aβ-dependent and independent manner, and different cellular sources of apoE4 may contribute in distinct ways to AD pathogenesis [4–8, 12–14, 21, 22].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [6]
In the citing paper
“Of the three alleles, APOEε3 is the most common in all human populations, present in almost 80% of individuals [57].”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [57]
In the citing paper
“APOEε4 is less frequent (~14%) among the general population but drastically increases risk for AD in a dose-dependent manner [54, 57]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [57]
In the citing paper
“Indeed, the ApoE4 isoform has been shown to affect lipid and glucose metabolism, but also many other processes involved in AD pathology including Aβ clearance, neuroinflammation, and synaptic function [5]”
From ApoE3 vs. ApoE4 Astrocytes: A Detailed Analysis Provides New Insights into Differences in Cholesterol Homeostasis (2022) · cites this paper as [5]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
Mild Cognitive Impairment: Clinical Characterization and Outcome
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999) · Archives of Neurology · doi:10.1001/archneur.56.3.303 · Cited by 8,980
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
Alzheimer's Disease Is a Synaptic Failure
Selkoe, D. J. (2002) · Science · doi:10.1126/science.1074069 · Cited by 4,420
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326
Blennow, K., de Leon, M. J., & Zetterberg, H. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69113-7 · Cited by 3,134
Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease
the European Alzheimer's Disease Initiative Investigators, Lambert, J.-C., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M., Combarros, O., Zelenika, D., Bullido, M. J., et al. (2009) · Nature Genetics · doi:10.1038/ng.439 · Cited by 2,234
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
Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model
Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G.-Q., & Mucke, L. (2007) · Science · doi:10.1126/science.1141736 · Cited by 1,892
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–255 of 255
Dalhaimer, P. (2019) · Cells · doi:10.3390/cells8090974 · Cited by 52
Update on the laboratory investigation of dyslipidemias
Ramasamy, I. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.01.015 · Cited by 50
Begcevic, I., Tsolaki, M., Brinc, D., Brown, M., Martinez-Morillo, E., Lazarou, I., Kozori, M., Tagaraki, F., Nenopoulou, S., Gkioka, M., et al. (2018) · F1000Research · doi:10.12688/f1000research.15095.1 · Cited by 51
Calcium-Sensing Receptors of Human Neural Cells Play Crucial Roles in Alzheimer's Disease
Chiarini, A., Armato, U., Liu, D., & Dal Prà, I. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00134 · Cited by 51
Beck, T. N., Nicolas, E., Kopp, M. C., & Golemis, E. A. (2014) · Oncoscience · doi:10.18632/oncoscience.64 · Cited by 50
Choi, J., Gao, J., Kim, J., Hong, C., Kim, J., & Tontonoz, P. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aad1904 · Cited by 49
Wang, Y.-Y., Ge, Y.-J., Tan, C.-C., Cao, X.-P., Tan, L., & Xu, W. (2021) · Journal of Alzheimer's Disease · doi:10.3233/jad-201606 · Cited by 49
HtrA1 Proteolysis of ApoE In Vitro Is Allele Selective
Chu, Q., Diedrich, J. K., Vaughan, J. M., Donaldson, C. J., Nunn, M. F., Lee, K.-F., & Saghatelian, A. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b03463 · Cited by 46
Genetic risk factors for Alzheimer disease: emerging roles of microglia in disease pathomechanisms
Takatori, S., Wang, W., Iguchi, A., & Tomita, T. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-05542-4_5 · Cited by 44
Astrocytic and neuronal apolipoprotein E isoforms differentially affect neuronal excitability
Konings, S. C., Torres-Garcia, L., Martinsson, I., & Gouras, G. K. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.734001 · Cited by 43
Hippocampal synaptic and neural network deficits in young mice carrying the humanAPOE 4 gene
Sun, G., He, Y., Ma, X. K., Li, S., Chen, D., Gao, M., Qiu, S., Yin, J., Shi, J., & Wu, J. (2017) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12720 · Cited by 42
Operto, G., Molinuevo, J. L., Cacciaglia, R., Falcon, C., Brugulat-Serrat, A., Suárez-Calvet, M., Grau-Rivera, O., Bargalló, N., Morán, S., Esteller, M., et al. (2019) · NeuroImage: Clinical · doi:10.1016/j.nicl.2019.101983 · Cited by 40
Genetics and Functional Imaging: Effects of APOE, BDNF, COMT, and KIBRA in Aging
Papenberg, G., Salami, A., Persson, J., Lindenberger, U., & Bäckman, L. (2015) · Neuropsychology Review · doi:10.1007/s11065-015-9279-8 · Cited by 39
Li, G., Kim, C., Kim, J., Yoon, H., Zhou, H., & Kim, J. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-150024 · Cited by 39
Chaudhry, A., & Rizig, M. (2021) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.117270 · Cited by 37
Correction: Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.32 · Cited by 32
Self-citationExtracellular Proteolysis of Apolipoprotein E (apoE) by Secreted Serine Neuronal Protease
Tamboli, I. Y., Heo, D., & Rebeck, G. W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093120 · Cited by 35
Hurtado, M. O., Kohler, I., & de Lange, E. C. M. (2018) · Bioanalysis · doi:10.4155/bio-2018-0135 · Cited by 34
Pankiewicz, J. E., Baquero-Buitrago, J., Sanchez, S., Lopez-Contreras, J., Kim, J., Sullivan, P. M., Holtzman, D. M., & Sadowski, M. J. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0156-1 · Cited by 34
“A single copy of the APOE ε4 allele endows a ~3 fold increase in AD risk, and 2 APOE ε4 copies result in a ~15 fold risk increase, while an APOE ε2 allele halves AD risk relative to 2 copies of ε3 (reviewed in [4]).”
BackgroundGallagher, D., Kiss, A., Lanctot, K. L., & Herrmann, N. (2018) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.18m12331 · Cited by 34
Kloske, C. M., Belloy, M. E., Blue, E. E., Bowman, G. R., Carrillo, M. C., Chen, X., Chiba‐Falek, O., Davis, A. A., Paolo, G. D., Garretti, F., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13877 · Cited by 33
Self-citationAPOE2 mitigates disease-related phenotypes in an isogenic hiPSC-based model of Alzheimer’s disease
Brookhouser, N., Raman, S., Frisch, C., Srinivasan, G., & Brafman, D. A. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01076-3 · Cited by 33
Integrated approach reveals diet, APOE genotype and sex affect immune response in APP mice
Nam, K. N., Wolfe, C. M., Fitz, N. F., Letronne, F., Castranio, E. L., Mounier, A., Schug, J., Lefterov, I., & Koldamova, R. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.10.018 · Cited by 32
Human APOE genotype affects intraneuronal A 1-42 accumulation in a lentiviral gene transfer model
Zhao, W., Dumanis, S. B., Tamboli, I. Y., Rodriguez, G. A., Jo LaDu, M., Moussa, C. E. H., & William Rebeck, G. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt525 · Cited by 32
Progress and challenges in the diagnosis of dementia: a critical review
Paraskevaidi, M., Martin-Hirsch, P. L., & Martin, F. L. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00007 · Cited by 31
Kong, Y., Huang, L., Li, W., Liu, X., Zhou, Y., Liu, C., Zhang, S., Xie, F., Zhang, Z., Jiang, D., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.609908 · Cited by 29
Self-citationAge stratification corrects bias in estimated hazard of APOE genotype for Alzheimer's disease
Liu, L., & Caselli, R. J. (2018) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.09.006 · Cited by 29
Tarawneh, R. (2023) · Biomolecules · doi:10.3390/biom13050830 · Cited by 29
Jones, N. S., Watson, K. Q., & Rebeck, G. W. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02256-2 · Cited by 26
Günaydin, C., Sondhi, D., Kaminsky, S. M., Lephart, H. C., Leopold, P. L., Hackett, N. R., Khanna, R., & Crystal, R. G. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.11.003 · Cited by 26
DNA Methylation Analysis of Candidate Genes Associated with Dementia in Peripheral Blood
Fransquet, P. D., Lacaze, P., Saffery, R., Phung, J., Parker, E., Shah, R. C., Murray, A., Woods, R. L., & Ryan, J. (2020) · Epigenomics · doi:10.2217/epi-2020-0236 · Cited by 25
Class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion
Dresselhaus, E., Duerr, J. M., Vincent, F., Sylvain, E. K., Beyna, M., Lanyon, L. F., LaChapelle, E., Pettersson, M., Bales, K. R., & Ramaswamy, G. (2018) · PLOS ONE · doi:10.1371/journal.pone.0194661 · Cited by 25
Association of shift work with incident dementia: a community-based cohort study
Liao, H., Pan, D., Deng, Z., Jiang, J., Cai, J., Liu, Y., He, B., Lei, M., Li, H., Li, Y., et al. (2022) · BMC Medicine · doi:10.1186/s12916-022-02667-9 · Cited by 24
Staurenghi, E., Leoni, V., Lo Iacono, M., Sottero, B., Testa, G., Giannelli, S., Leonarduzzi, G., & Gamba, P. (2022) · Antioxidants · doi:10.3390/antiox11112168 · Cited by 24
Montesanto, A., Crocco, P., Anfossi, M., Smirne, N., Puccio, G., Colao, R., Maletta, R., Passarino, G., Bruni, A. C., & Rose, G. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150993 · Cited by 24
Oblak, A. L., Kotredes, K. P., Pandey, R. S., Reagan, A. M., Ingraham, C., Perkins, B., Lloyd, C., Baker, D., Lin, P. B., Soni, D. M., et al. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.886575 · Cited by 23
Novel approaches to increase synaptic resilience as potential treatments for Alzheimer’s disease
Pham, A. Q., & Dore, K. (2023) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2022.03.032 · Cited by 21
Heneghan, A., Deng, F., Wells, K., Ritchie, K., Muniz-Terrera, G., Ritchie, C. W., Lawlor, B., & Naci, L. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-220267 · Cited by 18
Yuan, K., Longchamps, R. J., Pardiñas, A. F., Yu, M., Chen, T.-T., Lin, S.-C., Chen, Y., Lam, M., Liu, R., Xia, Y., et al. (2023) · doi:10.1101/2023.01.07.23284293 · Cited by 94
Huggins, L. K. L., Min, S. H., Kaplan, S., Wei, J., Welsh-Bohmer, K., & Xu, H. (2023) · Journal of Alzheimer's Disease · doi:10.3233/jad-221167 · Cited by 18
Self-citationMolecular mechanisms of Alzheimer’s disease: From therapeutic targets to promising drugs
Alan, E., Kerry, Z., & Sevin, G. (2023) · Fundamental & Clinical Pharmacology · doi:10.1111/fcp.12861 · Cited by 17
Li, H., Initiative, F. T. A. D. N., Liu, H., Lutz, M. W., & Luo, S. (2023) · Journal of Alzheimer's Disease · doi:10.3233/jad-220680 · Cited by 17
Tate, M., Wijeratne, H. R. S., Kim, B., Philtjens, S., You, Y., Lee, D., Gutierrez, D. A., Sharify, D., Wells, M., Perez‐Cardelo, M., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.14243 · Cited by 21
APOE-ε4-related differences in left thalamic microstructure in cognitively healthy adults
Mole, J. P., Fasano, F., Evans, J., Sims, R., Kidd, E., Aggleton, J. P., & Metzler-Baddeley, C. (2020) · Scientific Reports · doi:10.1038/s41598-020-75992-9 · Cited by 15
Therapeutic Idol reduction ameliorates amyloidosis and improves cognitive function in APP/PS1 mice
Gao, J., Littman, R., Diamante, G., Xiao, X., Ahn, I. S., Yang, X., Cole, T. A., & Tontonoz, P. (2020) · Molecular and Cellular Biology · doi:10.1128/mcb.00518-19 · Cited by 15
Supasitthumrong, T., Tunvirachaisakul, C., Aniwattanapong, D., Tangwongchai, S., Chuchuen, P., Tawankanjanachot, I., Snabboon, T., Hemrungrojn, S., Carvalho, A. F., & Maes, M. (2019) · Journal of Alzheimer’s Disease · doi:10.3233/jad-190114 · Cited by 13
Al‐Amin, M. M., Kim, B., Karahan, H., Tate, M. D., Walsh, S. P., Puntambekar, S. S., Bissel, S. J., Lamb, B. T., Wang, N., & Kim, J. (2025) · Alzheimer's & Dementia · doi:10.1002/alz.70791 · Cited by 6
Albright, J., & Initiative, A. D. N. (2019) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.07.001 · Cited by 104
APOE Genotype Influences Postprandial Blood Pressure After High fat Feeding in Older Adults
Stewart, K. C., Subramanian, D., Neal, U. J., & Hanson, A. J. (2019) · The Journal of nutrition, health and aging · doi:10.1007/s12603-019-1167-0 · Cited by 3
Andrieieva, D., Falltrick, I., Chiang, C.-Y., Beaumont, B., Guen, Y. L., Liu, C., Pergolesi, S., Ma, C.-T., Jackson, M. R., Hyman, B. T., et al. (2026) · doi:10.64898/2026.05.09.26352797 · Cited by 2
Self-citationDeep Trans-Omic Network Fusion for Molecular Mechanism of Alzheimer’s Disease
Xie, L., Raj, Y., Varathan, P., He, B., Yu, M., Nho, K., Salama, P., Saykin, A. J., & Yan, J. (2024) · Journal of Alzheimer's Disease · doi:10.3233/jad-240098 · Cited by 2
Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era
Coraglia, F., Cecchetti, G., Rugarli, G., Spinelli, E. G., Ghirelli, A., Pisano, S., Canu, E., Filippi, M., & Agosta, F. (2026) · Alzheimer's Research & Therapy · doi:10.1186/s13195-026-02089-2 · Cited by 1
Kopp, K., Silva, P., Damm, F., & Cosma, N. C. (2026) · Biomedicines · doi:10.3390/biomedicines14051012
Frisch, C., Baker, L., Srinivasan, G., Mintah, A. E., Leyasi, S., Pedroza, M., Galyon, B., & Brafman, D. A. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1856154
Jackson, R. J., Dierksmeier, S., Nishtar, M., Meltzer, J., Balduin, F., Beaumont, B., Fan, Z., Sergienko, E., Olson, S., Jackson, M. R., et al. (2026) · doi:10.64898/2026.06.09.730809
Metadata
- Authors
- Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G.
- Affiliations
- Xiamen University (CN)
- Mayo Clinic (US)
- Corresponding author
- Bu, Guojun
- Venue
- Nature Reviews Neurology
- Published
- 2013-01-08
- Volume
- 9
- Issue
- 2
- Pages
- 106-118
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- PMC
- PMC3726719
- OpenAlex
- W2140718540
- Cited by
- 3,459
- References
- 180
- Citations by year
- 2026: 273 · 2025: 343 · 2024: 332 · 2023: 277 · 2022: 331 · 2021: 341 · 2020: 321 · 2019: 291 · 2018: 278 · 2017: 206 · 2016: 171 · 2015: 128 · 2014: 123 · 2013: 41
- FWCI
- 17.01
- Type
- journal article
- Language
- en
- Update notices
- correction (2013-03-26)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- American Health Assistance Foundation
- Xiamen University
- National Institutes of Health
- National Institute on Aging (P01AG030128, R01AG044420, R01AG038710, R01AG027924, R01AG021173, R01AG031784, RF1AG046205, R01AG035355)
- National Institute of Neurological Disorders and Stroke (P01NS074969)
- 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, APOE ε4, Alzheimer's disease, genetic risk factors, amyloid-beta, neurodegeneration, cerebral amyloid angiopathy, neurovascular function, neuroinflammation, mitochondrial function
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Brain, Brain Injuries, Dementia, Humans, Immunotherapy, Inflammation, Neuronal Plasticity, Predictive Value of Tests, Risk, Vascular Diseases, Amyloid beta-Peptides, tau Proteins, Dendritic Spines, Lipid Metabolism, Neurogenesis, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
