ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies

Raulin, Ana-Caroline; Doss, Sydney V.; Trottier, Zachary A.; Ikezu, Tadafumi C.; Bu, Guojun; Liu, Chia-Chen

doi:10.1186/s13024-022-00574-4

Cited by 756Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies

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Raulin, Ana-Caroline, Doss, Sydney V., Trottier, Zachary A., Ikezu, Tadafumi C., Bu, Guojun, Liu, Chia-Chen·2022·Molecular Neurodegeneration

DOI 10.1186/s13024-022-00574-4PMC PMC9644639

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Abstract

Alzheimer’s disease (AD) is the most common cause of dementia worldwide, and its prevalence is rapidly increasing due to extended lifespans. Among the increasing number of genetic risk factors identified, the apolipoprotein E ( APOE ) gene remains the strongest and most prevalent, impacting more than half of all AD cases. While the ε4 allele of the APOE gene significantly increases AD risk, the ε2 allele is protective relative to the common ε3 allele. These gene alleles encode three apoE protein isoforms that differ at two amino acid positions. The primary physiological function of apoE is to mediate lipid transport in the brain and periphery; however, additional functions of apoE in diverse biological functions have been recognized. Pathogenically, apoE seeds amyloid-β (Aβ) plaques in the brain with apoE4 driving earlier and more abundant amyloids. ApoE isoforms also have differential effects on multiple Aβ-related or Aβ-independent pathways. The complexity of apoE biology and pathobiology presents challenges to designing effective apoE-targeted therapeutic strategies. This review examines the key pathobiological pathways of apoE and related targeting strategies with a specific focus on the latest technological advances and tools.

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In humans, three major isoforms of APOE are lipidated in an isoform-specific manner (ε2 > ε3 > ε4).
“In humans, three major isoforms of APOE are lipidated in an isoform‐specific manner (ε2 > ε3 > ε4). 9 , 48”
From Deletion of miR-33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice (2024) · cites this paper as [48]
The “APOE biology: synthesis, structure, and function” section identifies three major human apoE isoforms and says their differences affect lipid binding. “ApoE in dysregulation of lipid metabolism” reports an apoE2 > apoE3 > apoE4 ranking for cholesterol and phosphatidylcholine efflux in rat cells, not for the degree to which the isoforms are lipidated in humans. The claimed human lipidation ranking is therefore not established by these passages (page numbers unavailable). (LLM, conf=0.84)
Experimental — accuracy not yet measured
APOE binds to cell surface receptors including LDLR, LRP1, VLDLR, and APOER2.
“APOE binds to cell surface receptors, such as low‐density lipoprotein receptor (LDLR), LDLR‐related protein 1 (LRP1), very low‐density lipoprotein receptor (VLDLR), and apolipoprotein E receptor 2 (APOER2 or LRP8). 2 , 14 , 15”
From Deletion of neuronal Idol ameliorates Alzheimer's disease–related pathologies via APOE receptors (2025) · cites this paper as [2]
The “APOE biology: synthesis, structure, and function” section says apoE binds cell-surface receptors including LDLR and LRP1. The passages found do not identify VLDLR or APOER2 (LRP8) as apoE-binding receptors; the paper’s mention of VLDL refers to a lipoprotein, not its receptor. (LLM, conf=0.87)
Experimental — accuracy not yet measured
APOE is mainly secreted by astrocytes but is also expressed in microglia, neurons, and oligodendrocytes, particularly under injury and degenerative conditions.
“Although mainly secreted by astrocytes, APOE is also expressed in microglia, neurons, and oligodendrocytes, particularly under injury and degenerative conditions. 2 , 13”
From Deletion of neuronal Idol ameliorates Alzheimer's disease–related pathologies via APOE receptors (2025) · cites this paper as [2]
The Physiological function of apoE section says apoE expression rises in activated microglia and stressed neurons under pathological conditions and injury, and that oligodendrocytes express it more abundantly after injury. It also says astrocytes express and secrete apoE, but does not establish that astrocytes are its main source of secretion. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Genetic variants of many differentially expressed genes identified in this study, such as CLU and APOE, have been associated with increased Alzheimer's disease risk.
“Genetic variants of many of the differentially expressed genes identified in this study, such as CLU and APOE, have been associated with increased Alzheimer’s disease risk58,59.”
From mTORC1 drives cell-autonomous astrocyte reactivity in tuberous sclerosis (2026) · cites this paper as [59]
The section ‘ApoE isoform is a risk determinant for AD and related dementias’ states that APOE4 increases Alzheimer’s disease risk. The passages from this paper do not establish the corresponding risk association for CLU or for the broader group of genes named in the citing sentence. (LLM, conf=0.86)
Experimental — accuracy not yet measured
The APOE-ε4 allele increases Alzheimer's disease risk three- to eightfold compared to the neutral ε3 allele, while ε2 confers relative protection.
“The APOE-ε4 allele increases AD risk three- to eightfold compared to the neutral ε3 allele, while ε2 confers relative protection [154].”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [154]
The section “ApoE isoform is a risk determinant for AD and related dementias” (page unavailable) states that APOE4 increases AD risk and APOE2 reduces it by almost half. It does not give the claimed three- to eightfold increase relative to APOE3; instead, it reports an increase of up to 15-fold in APOE4 homozygotes. (LLM, conf=0.88)
Experimental — accuracy not yet measured

ApoE influences Alzheimer's disease pathogenesis through impaired clearance of Aβ by competing with receptor-mediated uptake (e.g., LRP1), modulation of tau phosphorylation and spread, and regulation of microglial activation.
“ApoE influences AD pathogenesis through multiple pathways, such as (i) impaired clearance of Aβ by competing with receptor-mediated uptake (e.g., LRP1), (ii) modulation of tau phosphorylation and spread, and (iii) regulation of microglial activation.”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [154]
The ‘ApoE and Aβ’ section describes competition for Aβ receptor-binding sites and impaired receptor-mediated clearance involving LRP1, particularly with apoE4. The ‘ApoE and tau’ and ‘ApoE and neuroinflammation’ sections support effects on tau phosphorylation and microglial responses, respectively. The copy discusses tau deposition and aggregation, but the passages found do not establish an effect on tau spread. (LLM, conf=0.86)
Experimental — accuracy not yet measured
APOE is multifunctional, with roles in lipid and glucose metabolism, neuroinflammation, amyloid and tau accumulation, and blood-brain barrier dysfunction.
“APOE is multifunctional, with roles in lipid and glucose metabolism, neuroinflammation, amyloid and tau accumulation, and blood-brain barrier dysfunction [2].”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [2]
APOE influences Alzheimer's disease-related pathologies including Aβ accumulation, tauopathy, neuroinflammation, and synaptic impairment.
“These efforts have resulted in identifying multiple mechanisms by which APOE influences AD‐related pathologies, including amyloid beta (Aβ) accumulation, tauopathy, neuroinflammation, and synaptic impairment. 2”
From Deletion of neuronal Idol ameliorates Alzheimer's disease–related pathologies via APOE receptors (2025) · cites this paper as [2]
APOE is increasingly viewed not only as a risk locus, but also as a mechanistically actionable therapeutic axis in AD.
“as APOE is increasingly viewed not only as a risk locus, but also as a mechanistically actionable therapeutic axis in AD 2 .”
From Association of Rare APOE Missense Variants R189C and W276C With Risk of Alzheimer Disease (2026) · cites this paper as [2]
C-terminal ApoE biology, including lipidation and self-association, is not merely correlative but is closely tied to pathogenesis and may inform future APOE-directed therapeutic strategies.
“Together, these data support a model in which C-terminal ApoE biology, including lipidation and self-association, is not merely correlative but is closely tied to pathogenesis and may inform future APOE-directed therapeutic strategies 2,17 .”
From Association of Rare APOE Missense Variants R189C and W276C With Risk of Alzheimer Disease (2026) · cites this paper as [2]
The APOE gene plays a central role in modulating Alzheimer's disease risk through lipid transport, synaptic function, and amyloid-beta metabolism in the brain.
“Among these, the APOE gene plays a central role in modulating disease risk, primarily through its involvement in lipid transport, synaptic function, and amyloid-beta metabolism in the brain (Martens et al., 2022; Raulin et al., 2022).”
From Isogenic human stem cell models reveal mutation-dependent protective mechanisms of APOE3 Christchurch (2026) · cites this paper as Raulin et al., 2022
The Aβ changes suggest distinct biochemical interactions influencing Aβ deposition or clearance.
“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 [2]
Sporadic Alzheimer's disease is strongly associated with polymorphisms in the APOE gene.
“In contrast, sporadic AD is strongly associated with polymorphisms in the APOE gene.”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [154]
APOE variants modulate amyloid deposition, reshape immune responses and lipid metabolism, and position APOE at the nexus of amyloid, tau, and neuroinflammation.
“Recent work suggests that APOE variants not only modulate amyloid deposition but also reshape immune responses and lipid metabolism, positioning APOE at the nexus of amyloid, tau, and neuroinflammation [154].”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [154]
APOE4 isoform has been identified as the strongest genetic risk factor for late-onset AD.
“APOE exists in three isoforms, namely APOE2, APOE3, and APOE4, among which APOE4 isoform has been identified as the strongest genetic risk factor for late-onset AD.173”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [173]

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2 retracted

Retracted: Effects of microRNA‐10a on synapse remodeling in hippocampal neurons and neuronal cell proliferation and apoptosis through the BDNF‐TrkB signaling pathway in a rat model of Alzheimer's disease
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Retracted
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Profile and Regulation of Apolipoprotein E (ApoE) Expression in the CNS in Mice with Targeting of Green Fluorescent Protein Gene to the ApoE Locus
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Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model
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Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation.
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APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia
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Aducanumab: Appropriate Use Recommendations
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The identity and function of microglia in neurodegeneration
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Decreased Melatonin Levels in Postmortem Cerebrospinal Fluid in Relation to Aging, Alzheimer’s Disease, and Apolipoprotein E-ε4/4 Genotype1
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Apolipoprotein E distribution among human plasma lipoproteins: role of the cysteine-arginine interchange at residue 112
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Apolipoprotein E–dependent accumulation of Alzheimer disease–related lesions begins in middle age
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ApoE facilitates the microglial response to amyloid plaque pathology
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Apolipoprotein E, Especially Apolipoprotein E4, Increases the Oligomerization of Amyloid β Peptide
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“The findings of earlier Aβ deposition [87], greater Aβ oligomerization, and lower CSF and plasma Aβ levels in human APOE4 carriers [88, 89] strongly support the idea that apoE isoforms differentially regulate Aβ fibril formation via its interaction with Aβ, and that this interaction may represent a potential target fo…”
Background
Topology of human apolipoprotein E3 uniquely regulates its diverse biological functions
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Reconstruction of the human blood–brain barrier in vitro reveals a pathogenic mechanism of APOE4 in pericytes
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Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism
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Neuronal Clearance of Amyloid-β by Endocytic Receptor LRP1
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The Role of APOE4 in Disrupting the Homeostatic Functions of Astrocytes and Microglia in Aging and Alzheimer’s Disease
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HumanAPOEIsoform-Dependent Effects on Brain β-Amyloid Levels in PDAPP Transgenic Mice
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Astrocytic LRP1 Mediates Brain Aβ Clearance and Impacts Amyloid Deposition
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Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer's disease
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Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
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“While apoE expression in the brain was first described in astrocytes, it has been found to be drastically up regulated in activated microglia and in stressed neurons under pathological conditions and injury [34, 36, 63, 64].”
Background
Association of Apolipoprotein E ε4 With Medial Temporal Tau Independent of Amyloid-β
Therriault, J., Benedet, A. L., Pascoal, T. A., Mathotaarachchi, S., Chamoun, M., Savard, M., Thomas, E., Kang, M. S., Lussier, F., Tissot, C., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2019.4421 · Cited by 256 · see citing works
Apolipoprotein E exhibits isoform‐specific promotion of lipid efflux from astrocytes and neurons in culture
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“In rat primary astrocytes and neurons, recombinant apoE2 was more efficient at promoting the efflux of cholesterol and phosphatidylcholine (PC), followed by apoE3, and then apoE4 [132].”
Background
Apolipoprotein E: Diversity of Cellular Origins, Structural and Biophysical Properties, and Effects in Alzheimer's Disease
Huang, Y., Weisgraber, K. H., Mucke, L., & Mahley, R. W. (2004) · Journal of Molecular Neuroscience · doi:10.1385/jmn:23:3:189 · Cited by 242 · see citing works
APOE and TREM2 regulate amyloid-responsive microglia in Alzheimer’s disease
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Evaluation of Aducanumab for Alzheimer Disease: Scientific Evidence and Regulatory Review Involving Efficacy, Safety, and Futility
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Association of Chronic Low-grade Inflammation With Risk of Alzheimer Disease in ApoE4 Carriers
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“Contrary to this trend in genotype, cumulative incidence of AD was shown to markedly increase as levels of serum CRP increase, with the greatest effect in APOE4 carriers [126].”
Evidence for impaired amyloid β clearance in Alzheimer's disease
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miR-132/212 deficiency impairs tau metabolism and promotes pathological aggregation in vivo
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Alzheimer’s Risk Factors Age, APOE Genotype, and Sex Drive Distinct Molecular Pathways
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Endo-lysosomal dysregulations and late-onset Alzheimer’s disease: impact of genetic risk factors
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A blood-based diagnostic test incorporating plasma Aβ42/40 ratio, ApoE proteotype, and age accurately identifies brain amyloid status: findings from a multi cohort validity analysis
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Plasma Biomarkers Associated With the Apolipoprotein E Genotype and Alzheimer Disease
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Glial fibrillary acidic protein-apolipoprotein E (apoE) transgenic mice: astrocyte-specific expression and differing biological effects of astrocyte-secreted apoE3 and apoE4 lipoproteins.
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Melatonin regulates Aβ production/clearance balance and Aβ neurotoxicity: A potential therapeutic molecule for Alzheimer’s disease
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APOE ε4 is associated with severity of Lewy body pathology independent of Alzheimer pathology
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Site-specific mutagenesis of human apolipoprotein E. Receptor binding activity of variants with single amino acid substitutions.
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Apolipoprotein E4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for Alzheimer disease
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Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of β-amyloidosis
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The apoE isoform binding properties of the VLDL receptor reveal marked differences from LRP and the LDL receptor.
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Haploinsufficiency of Human APOE Reduces Amyloid Deposition in a Mouse Model of Amyloid-β Amyloidosis
Kim, J., Jiang, H., Park, S., Eltorai, A. E. M., Stewart, F. R., Yoon, H., Basak, J. M., Finn, M. B., & Holtzman, D. M. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3773-11.2011 · Cited by 199 · cited 1× · see citing works
“ApoE haploinsufficiency was shown to reduce amyloid deposition in amyloid model mice [191].”
Background
Aducanumab: Appropriate Use Recommendations Update
Cummings, J. L., Rabinovici, G. D., Atri, A., Aisen, P. S. S., Apostolova, L. G., Hendrix, S. B., Sabbagh, M. N., Selkoe, D. J., Weiner, M. W., & Salloway, S. (2022) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2022.34 · Cited by 198 · see citing works
Plaque-associated human microglia accumulate lipid droplets in a chimeric model of Alzheimer’s disease
Claes, C., Danhash, E. P., Hasselmann, J., Chadarevian, J. P., Shabestari, S. K., England, W. E., Lim, T. E., Hidalgo, J. L. S., Spitale, R. C., Davtyan, H., et al. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00473-0 · Cited by 197 · see citing works
Human APOE4 increases microglia reactivity at Aβ plaques in a mouse model of Aβ deposition
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Modified ketogenic diet is associated with improved cerebrospinal fluid biomarker profile, cerebral perfusion, and cerebral ketone body uptake in older adults at risk for Alzheimer’s disease: a pilot study
Neth, B., Mintz, A., Whitlow, C. T., Jung, Y., Sai, K., Register, T., Kellar, D., Lockhart, S., Hoscheidt, S., Maldjian, J., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.09.015 · Cited by 191 · see citing works
Gut mycobiome and its interaction with diet, gut bacteria and alzheimer's disease markers in subjects with mild cognitive impairment: A pilot study
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Double-blind, placebo-controlled, proof-of-concept trial of bexarotene in moderate Alzheimer’s disease
Cummings, J. L., Zhong, K., Kinney, J. W., Heaney, C., Moll-Tudla, J., Joshi, A., Pontecorvo, M., Devous, M., Tang, A., & Bena, J. (2016) · Alzheimer's Research & Therapy · doi:10.1186/s13195-016-0173-2 · Cited by 190 · see citing works
Apolipoprotein E isoform-specific regulation of dendritic spine morphology in apolipoprotein E transgenic mice and Alzheimer's disease patients
Ji, Y., Gong, Y., Gan, W., Beach, T., Holtzman, D. M., & Wisniewski, T. (2003) · Neuroscience · doi:10.1016/j.neuroscience.2003.08.007 · Cited by 189 · see citing works
APOE4 accelerates advanced-stage vascular and neurodegenerative disorder in old Alzheimer’s mice via cyclophilin A independently of amyloid-β
Montagne, A., Nikolakopoulou, A. M., Huuskonen, M. T., Sagare, A. P., Lawson, E. J., Lazic, D., Rege, S. V., Grond, A., Zuniga, E., Barnes, S. R., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00073-z · Cited by 188 · see citing works
Gene Transfer of Human Apoe Isoforms Results in Differential Modulation of Amyloid Deposition and Neurotoxicity in Mouse Brain
Hudry, E., Dashkoff, J., Roe, A. D., Takeda, S., Koffie, R. M., Hashimoto, T., Scheel, M., Spires-Jones, T., Arbel-Ornath, M., Betensky, R., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3007000 · Cited by 187 · see citing works
NEBULA is a fast negative binomial mixed model for differential or co-expression analysis of large-scale multi-subject single-cell data
He, L., Davila-Velderrain, J., Sumida, T. S., Hafler, D. A., Kellis, M., & Kulminski, A. M. (2021) · Communications Biology · doi:10.1038/s42003-021-02146-6 · Cited by 181 · see citing works
Neuronal heparan sulfates promote amyloid pathology by modulating brain amyloid-β clearance and aggregation in Alzheimer’s disease
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APOE immunotherapy reduces cerebral amyloid angiopathy and amyloid plaques while improving cerebrovascular function
Xiong, M., Jiang, H., Serrano, J. R., Gonzales, E. R., Wang, C., Gratuze, M., Hoyle, R., Bien-Ly, N., Silverman, A. P., Sullivan, P. M., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abd7522 · Cited by 179 · see citing works
Apolipoprotein E ε4 is associated with disease-specific effects on brain atrophy in Alzheimer's disease and frontotemporal dementia
Agosta, F., Vossel, K. A., Miller, B. L., Migliaccio, R., Bonasera, S. J., Filippi, M., Boxer, A. L., Karydas, A., Possin, K. L., & Gorno-Tempini, M. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812697106 · Cited by 178 · see citing works
Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation
Liao, F., Li, A., Xiong, M., Bien-Ly, N., Jiang, H., Zhang, Y., Finn, M. B., Hoyle, R., Keyser, J., Lefton, K. B., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96429 · Cited by 178 · see citing works
APOE genotype regulates pathology and disease progression in synucleinopathy
Davis, A. A., Inman, C. E., Wargel, Z. M., Dube, U., Freeberg, B. M., Galluppi, A., Haines, J. N., Dhavale, D. D., Miller, R., Choudhury, F. A., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay3069 · Cited by 177 · see citing works
<scp> APOE </scp> ε2 is associated with milder clinical and pathological <scp>A</scp> lzheimer disease
Serrano‐Pozo, A., Qian, J., Monsell, S. E., Betensky, R. A., & Hyman, B. T. (2015) · Annals of Neurology · doi:10.1002/ana.24369 · Cited by 176 · see citing works
Mechanisms of Melatonin in Alleviating Alzheimer’s Disease
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AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease
Rosenberg, J. B., Kaplitt, M. G., De, B. P., Chen, A., Flagiello, T., Salami, C., Pey, E., Zhao, L., Ricart Arbona, R. J., Monette, S., et al. (2018) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2017.231 · Cited by 169 · cited 1× · see citing works
“Although there are certainly hesitations regarding CNS delivery of AAVs in humans, work in non-human primates has proven this method to be safe and effective in promoting widespread expression of apoE2 [225].”
Background
Peripheral apoE4 enhances Alzheimer’s pathology and impairs cognition by compromising cerebrovascular function
Liu, C.-C., Zhao, J., Fu, Y., Inoue, Y., Ren, Y., Chen, Y., Doss, S. V., Shue, F., Jeevaratnam, S., Bastea, L., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01127-0 · Cited by 168 · see citing works
Self-citation
Blocking the apolipoprotein E/amyloid-β interaction as a potential therapeutic approach for Alzheimer's disease
Sadowski, M. J., Pankiewicz, J., Scholtzova, H., Mehta, P. D., Prelli, F., Quartermain, D., & Wisniewski, T. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604011103 · Cited by 167 · see citing works
Apolipoprotein E as a Therapeutic Target in Alzheimer’s Disease: A Review of Basic Research and Clinical Evidence
Yamazaki, Y., Painter, M. M., Bu, G., & Kanekiyo, T. (2016) · CNS Drugs · doi:10.1007/s40263-016-0361-4 · Cited by 166 · see citing works
Self-citation
Therapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease
Williams, T., Borchelt, D., & Chakrabarty, P. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-0358-9 · Cited by 166 · see citing works
Levels of Soluble Apolipoprotein E/Amyloid-β (Aβ) Complex Are Reduced and Oligomeric Aβ Increased with APOE4 and Alzheimer Disease in a Transgenic Mouse Model and Human Samples*
Tai, L. M., Bilousova, T., Jungbauer, L., Roeske, S. K., Youmans, K. L., Yu, C., Poon, W. W., Cornwell, L. B., Miller, C. A., Vinters, H. V., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.442103 · Cited by 165 · see citing works
Self-citation
Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation
Farmer, B., Kluemper, J., & Johnson, L. (2019) · Cells · doi:10.3390/cells8020182 · Cited by 164 · see citing works
Expression and secretion of <scp>apoE</scp> isoforms in astrocytes and microglia during inflammation
Lanfranco, M. F., Sepulveda, J., Kopetsky, G., & Rebeck, G. W. (2021) · Glia · doi:10.1002/glia.23974 · Cited by 164 · see citing works
Small Molecule Structure Correctors Abolish Detrimental Effects of Apolipoprotein E4 in Cultured Neurons
Chen, H.-K., Liu, Z., Meyer-Franke, A., Brodbeck, J., Miranda, R. D., McGuire, J. G., Pleiss, M. A., Ji, Z.-S., Balestra, M. E., Walker, D. W., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.276162 · Cited by 163 · see citing works
Opposing effects of viral mediated brain expression of apolipoprotein E2 (apoE2) and apoE4 on apoE lipidation and Aβ metabolism in apoE4-targeted replacement mice
Hu, J., Liu, C.-C., Chen, X.-F., Zhang, Y.-W., Xu, H., & Bu, G. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0001-3 · Cited by 161 · see citing works
Self-citation
Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis
Kim, J., Eltorai, A. E. M., Jiang, H., Liao, F., Verghese, P. B., Kim, J., Stewart, F. R., Basak, J. M., & Holtzman, D. M. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20121274 · Cited by 160 · cited 1× · see citing works
“3, a monoclonal antibody specific against apoE, is effective in reducing amyloid deposition by modulating microglial responses and inflammatory cytokine levels [193].”
Background
Apolipoprotein E2-Christchurch (136 Arg----Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia.
Wardell, M. R., Brennan, S. O., Janus, E. D., Fraser, R., & Carrell, R. W. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113096 · Cited by 159 · cited 2× · see citing works
“APOE3-Ch was discovered in 1987 as a susceptibility factor for type III hyperlipoproteinemia in Caucasian populations [180].”
Background
APOE modifies the association between Aβ load and cognition in cognitively normal older adults
Kantarci, K., Lowe, V. J., Przybelski, S. A., Weigand, S. D., Senjem, M. L., Ivnik, R. J., Preboske, G. M., Roberts, R. O., Geda, Y. E., Boeve, B. F., et al. (2011) · Neurology · doi:10.1212/wnl.0b013e31824365ab · Cited by 159 · see citing works
Heparan Sulfate Proteoglycans Participate in Hepatic Lipaseand Apolipoprotein E-mediated Binding and Uptake of Plasma Lipoproteins, Including High Density Lipoproteins
Ji, Z.-S., Dichek, H. L., Miranda, R. D., & Mahley, R. W. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.50.31285 · Cited by 156 · see citing works
APOE4 exacerbates α-synuclein pathology and related toxicity independent of amyloid
Zhao, N., Attrebi, O. N., Ren, Y., Qiao, W., Sonustun, B., Martens, Y. A., Meneses, A. D., Li, F., Shue, F., Zheng, J., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay1809 · Cited by 156 · see citing works
Self-citation
Melatonin Reverses the Profibrillogenic Activity of Apolipoprotein E4 on the Alzheimer Amyloid Aβ Peptide
Pöeggeler, B., Miravalle, L., Zagorski, M. G., Wısnıewskı, T., Chyan, Y., Zhang, Y., Shao, H., Bryant‐Thomas, T., Vidal, R., Frangione, B., et al. (2001) · Biochemistry · doi:10.1021/bi0114269 · Cited by 154 · see citing works
The Important Interface Between Apolipoprotein E and Neuroinflammation in Alzheimer’s Disease
Kloske, C. M., & Wilcock, D. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00754 · Cited by 152 · see citing works
Increased tau Phosphorylation in Apolipoprotein E4 Transgenic Mice Is Associated with Activation of Extracellular Signal-regulated Kinase
Harris, F. M., Brecht, W. J., Xu, Q., Mahley, R. W., & Huang, Y. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408127200 · Cited by 151 · see citing works
Longitudinal brain imaging in preclinical Alzheimer disease: impact of APOE ε4 genotype
Mishra, S., Blazey, T. M., Holtzman, D. M., Cruchaga, C., Su, Y., Morris, J. C., Benzinger, T. L. S., & Gordon, B. A. (2018) · Brain · doi:10.1093/brain/awy103 · Cited by 151 · see citing works
APOE-ε2 and APOE-ε4 Correlate With Increased Amyloid Accumulation in Cerebral Vasculature
Nelson, P. T., Pious, N. M., Jicha, G. A., Wilcock, D. M., Fardo, D. W., Estus, S., & Rebeck, G. W. (2013) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31829a25b9 · Cited by 150 · see citing works
The ketogenic diet as a potential treatment and prevention strategy for Alzheimer's disease
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The Binding of Apolipoprotein E to Oligomers and Fibrils of Amyloid-β Alters the Kinetics of Amyloid Aggregation
Garai, K., Verghese, P. B., Baban, B., Holtzman, D. M., & Frieden, C. (2014) · Biochemistry · doi:10.1021/bi5008172 · Cited by 145 · see citing works
APOE alleles and diet in brain aging and Alzheimer's disease
Yassine, H. N., & Finch, C. E. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00150 · Cited by 145 · see citing works
A randomized, controlled clinical trial of plasma exchange with albumin replacement for Alzheimer's disease: Primary results of the AMBAR Study
Boada, M., López, O. L., Olazarán, J., Núñez, L., Pfeffer, M., Paricio, M., Lorites, J., Piñol‐Ripoll, G., Gámez, J. E., Anaya, F., et al. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12137 · Cited by 143 · see citing works
Neuronal apolipoprotein E4 increases cell death and phosphorylated tau release in alzheimer disease
Wadhwani, A. R., Affaneh, A., Van Gulden, S., & Kessler, J. A. (2019) · Annals of Neurology · doi:10.1002/ana.25455 · Cited by 142 · see citing works
Correlation of diet, microbiota and metabolite networks in inflammatory bowel disease
Yi, W., Gan, H. Y., Li, X., Huang, Y., Li, Z. C., Deng, H., Chen, S. Z., Zhou, Y. J., Wang, L. S., Han, Y. P., et al. (2019) · Journal of Digestive Diseases · doi:10.1111/1751-2980.12795 · Cited by 142 · see citing works
Apolipoprotein E gene polymorphism and risk of type 2 diabetes and cardiovascular disease
El-Lebedy, D. H., Raslan, H. M., & Mohammed, A. M. (2016) · Cardiovascular Diabetology · doi:10.1186/s12933-016-0329-1 · Cited by 139 · see citing works
APOE ε2 is associated with increased tau pathology in primary tauopathy
Zhao, N., Liu, C.-C., Van Ingelgom, A. J., Linares, C., Kurti, A., Knight, J. A., Heckman, M. G., Diehl, N. N., Shinohara, M., Martens, Y. A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06783-0 · Cited by 139 · cited 2× · see citing works
“The isoform-specific interactions between apoE and tau have become of interest not only in AD research, but also for other tauopathies such as frontotemporal dementia (FTD), chronic traumatic encephalopathy (CTE), and corticobasal degeneration (CBD) [103, 106, 108, 109].”
BackgroundSelf-citation
Lack of hepatic apoE does not influence early Aβ deposition: observations from a new APOE knock-in model
Huynh, T.-P. V., Wang, C., Tran, A. C., Tabor, G. T., Mahan, T. E., Francis, C. M., Finn, M. B., Spellman, R., Manis, M., Tanzi, R. E., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0337-1 · Cited by 139 · see citing works
Overexpressing low‐density lipoprotein receptor reduces tau‐associated neurodegeneration in relation to apoE‐linked mechanisms
Shi, Y., Andhey, P. S., Ising, C., Wang, K., Snipes, L. L., Boyer, K., Lawson, S., Yamada, K., Qin, W., Manis, M., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.05.034 · Cited by 135 · see citing works
Brain delivery of supplemental docosahexaenoic acid (DHA): A randomized placebo-controlled clinical trial
Arellanes, I. C., Choe, N., Solomon, V. A., He, X., Kavin, B., Martinez, A. E., Kono, N., Buennagel, D. P., Hazra, N., Kim, G., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102883 · Cited by 134 · see citing works
Selective reduction of astrocyte apoE3 and apoE4 strongly reduces Aβ accumulation and plaque-related pathology in a mouse model of amyloidosis
Mahan, T. E., Wang, C., Bao, X., Choudhury, A., Ulrich, J. D., & Holtzman, D. M. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00516-0 · Cited by 134 · see citing works
The promise of microRNA-based therapies in Alzheimer’s disease: challenges and perspectives
Walgrave, H., Zhou, L., Strooper, B. D., & Salta, E. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00496-7 · Cited by 132 · see citing works
Apolipoprotein E4 impairs the response of neurodegenerative retinal microglia and prevents neuronal loss in glaucoma
Margeta, M. A., Yin, Z., Madore, C., Pitts, K. M., Letcher, S. M., Tang, J., Jiang, S., Gauthier, C. D., Silveira, S. R., Schroeder, C. M., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.07.014 · Cited by 130 · see citing works
Dietary inulin alters the gut microbiome, enhances systemic metabolism and reduces neuroinflammation in an APOE4 mouse model
Hoffman, J. D., Yanckello, L. M., Chlipala, G. E., Hammond, T. C., McCulloch, S. D., Parikh, I. J., Sun, S., Morganti, J. M., Green, S. J., & Lin, A. (2019) · PLoS ONE · doi:10.1371/journal.pone.0221828 · Cited by 129 · see citing works
Phospholipids of APOE lipoproteins activate microglia in an isoform-specific manner in preclinical models of Alzheimer’s disease
Fitz, N. F., Nam, K. N., Wolfe, C. M., Letronne, F., Playso, B. E., Iordanova, B. E., Kozai, T. D. Y., Biedrzycki, R. J., Kagan, V. E., Tyurina, Y. Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23762-0 · Cited by 129 · see citing works
Anti-ApoE Antibody Given after Plaque Onset Decreases Aβ Accumulation and Improves Brain Function in a Mouse Model of Aβ Amyloidosis
Liao, F., Hori, Y., Hudry, E., Bauer, A. Q., Jiang, H., Mahan, T. E., Lefton, K. B., Zhang, T. J., Dearborn, J. T., Kim, J., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0646-14.2014 · Cited by 128 · cited 1× · see citing works
“3 to amyloid model mice reduces Aβ pathology, improves spatial learning performance, and restores functional connectivity without altering plasma cholesterol levels when administered both prior to and after plaque onset [194].”
Background
microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain
Kim, J., Yoon, H., Horie, T., Burchett, J. M., Restivo, J. L., Rotllan, N., Ramírez, C. M., Verghese, P. B., Ihara, M., Hoe, H.-S., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2053-15.2015 · Cited by 128 · cited 1× · see citing works
“Targeting of miRNA-33 via ASO results in increased ABCA1 levels, elevated apoE lipidation, and decreased Aβ levels in mouse models [233].”
Background
Apolipoprotein E and Peptide Mimetics Modulate Inflammation by Binding the SET Protein and Activating Protein Phosphatase 2A
Christensen, D. J., Ohkubo, N., Oddo, J., Van Kanegan, M. J., Neil, J., Li, F., Colton, C. A., & Vitek, M. P. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002847 · Cited by 125 · see citing works
APOE genotype and early β-amyloid accumulation in older adults without dementia
Lim, Y. Y., Mormino, E. C., Initiative, F. T. A. D. N., Initiative, A. D. N., Weiner, M., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000004336 · Cited by 125 · see citing works
Presence of an APOE4 allele results in significantly earlier onset of Parkinson's disease and a higher risk with dementia
Pankratz, N., Byder, L., Halter, C. A., Rudolph, A., Shults, C. W., Conneally, P. M., Foroud, T., & Nichols, W. C. (2005) · Movement Disorders · doi:10.1002/mds.20663 · Cited by 123 · see citing works
First AAV gene therapy poised for landmark approval
Smalley, E. (2017) · Nature Biotechnology · doi:10.1038/nbt1117-998 · Cited by 121 · see citing works
Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Mediates Neuronal Aβ42 Uptake and Lysosomal Trafficking
Fuentealba, R. A., Liu, Q., Zhang, J., Kanekiyo, T., Hu, X., Lee, J.-M., LaDu, M. J., & Bu, G. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011884 · Cited by 116 · see citing works
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ABCA1 Agonist Reverses the ApoE4-Driven Cognitive and Brain Pathologies
Boehm-Cagan, A., Bar, R., Liraz, O., Bielicki, J. K., Johansson, J. O., & Michaelson, D. M. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-160467 · Cited by 116 · see citing works
Microbial involvement in Alzheimer disease development and progression
Bulgart, H. R., Neczypor, E. W., Wold, L. E., & Mackos, A. R. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00378-4 · Cited by 116 · see citing works
Disturbed Sleep Patterns in Elders with Mild Cognitive Impairment: The Role of Memory Decline and ApoE ε 4 Genotype
Hita-Yáñez, E., Atienza, M., Gil-Neciga, E., & Cantero, J. L. (2012) · Current Alzheimer Research · doi:10.2174/156720512800107609 · Cited by 115 · see citing works
Genetic Restoration of Plasma ApoE Improves Cognition and Partially Restores Synaptic Defects in ApoE-Deficient Mice
Lane-Donovan, C., Wong, W. M., Durakoglugil, M. S., Wasser, C. R., Jiang, S., Xian, X., & Herz, J. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.1054-16.2016 · Cited by 115 · see citing works
Melatonin for Sleep Disorders and Cognition in Dementia
Xu, J., Wang, L., Dammer, E. B., Li, C., Xu, G., Chen, S., & Wang, G. (2015) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317514568005 · Cited by 114 · see citing works
Reduced levels of human apoE4 protein in an animal model of cognitive impairment
Sullivan, P. M., Han, B., Liu, F., Mace, B. E., Ervin, J. F., Wu, S., Koger, D., Paul, S., & Bales, K. R. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.05.011 · Cited by 113 · see citing works
Role of phosphatidylcholine‐DHA in preventing APOE4‐associated Alzheimer's disease
Patrick, R. P. (2018) · The FASEB Journal · doi:10.1096/fj.201801412r · Cited by 112 · see citing works
The Genetics of Alzheimer’s Disease
Barber, R. C. (2012) · Scientifica · doi:10.6064/2012/246210 · Cited by 111 · see citing works
APOE2 eases cognitive decline during Aging: Clinical and preclinical evaluations
Shinohara, M., Kanekiyo, T., Yang, L., Linthicum, D., Shinohara, M., Fu, Y., Price, L., Frisch‐Daiello, J. L., Han, X., Fryer, J. D., et al. (2016) · Annals of Neurology · doi:10.1002/ana.24628 · Cited by 111 · see citing works
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Central and Peripheral Metabolic Defects Contribute to the Pathogenesis of Alzheimer's Disease: Targeting Mitochondria for Diagnosis and Prevention
Peng, Y., Gao, P., Shi, L., Chen, L., Liu, J., & Long, J. (2020) · Antioxidants & Redox Signaling · doi:10.1089/ars.2019.7763 · Cited by 110 · see citing works
Safety, Tolerability, and Feasibility of Young Plasma Infusion in the Plasma for Alzheimer Symptom Amelioration Study: A Randomized Clinical Trial
Sha, S. J., Deutsch, G. K., Tian, L., Richardson, K., Coburn, M., Gaudioso, J. L., Marcal, T., Solomon, E., Boumis, A., Bet, A., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2018.3288 · Cited by 109 · see citing works
Increased Expression of Neuronal Apolipoprotein E in Human Brain With Cerebral Infarction
Aoki, K., Uchihara, T., Sanjo, N., Nakamura, A., Ikeda, K., Tsuchiya, K., & Wakayama, Y. (2003) · Stroke · doi:10.1161/01.str.0000064320.73388.c6 · Cited by 108 · see citing works
APOE3 -Jacksonville (V236E) variant reduces self-aggregation and risk of dementia
Liu, C.-C., Murray, M. E., Li, X., Zhao, N., Wang, N., Heckman, M. G., Shue, F., Martens, Y., Li, Y., Raulin, A.-C., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abc9375 · Cited by 108 · see citing works
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Exercise, APOE, and working memory: MEG and behavioral evidence for benefit of exercise in epsilon4 carriers
Deeny, S. P., Poeppel, D., Zimmerman, J. B., Roth, S. M., Brandauer, J., Witkowski, S., Hearn, J. W., Ludlow, A. T., Contreras-Vidal, J. L., Brandt, J., et al. (2008) · Biological Psychology · doi:10.1016/j.biopsycho.2008.02.007 · Cited by 107 · see citing works
Cholesterol, Atherosclerosis, and APOE in Vascular Contributions to Cognitive Impairment and Dementia (VCID): Potential Mechanisms and Therapy
Duong, M. T., Nasrallah, I. M., Wolk, D. A., Chang, C. C. Y., & Chang, T. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.647990 · Cited by 106 · see citing works
Amino-terminal domain stability mediates apolipoprotein E aggregation into neurotoxic fibrils
Hatters, D. M., Zhong, N., Rutenber, E., & Weisgraber, K. H. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.06.080 · Cited by 105 · see citing works
Comparative profiling of the synaptic proteome from Alzheimer’s disease patients with focus on the APOE genotype
Hesse, R., Hurtado, M. L., Jackson, R. J., Eaton, S. L., Herrmann, A. G., Colom‐Cadena, M., Tzioras, M., King, D., Rose, J. L., Tulloch, J., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0847-7 · Cited by 103 · see citing works
Premorbid effects of APOE on synaptic proteins in human temporal neocortex
Love, S., Siew, L. K., Dawbarn, D., Wilcock, G. K., Ben‐Shlomo, Y., & Allen, S. J. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.04.008 · Cited by 101 · see citing works
Inhibition of the canonical Wnt signaling pathway by apolipoprotein E4 in PC12 cells
Caruso, A., Motolese, M., Iacovelli, L., Caraci, F., Copani, A., Nicoletti, F., Terstappen, G. C., Gaviraghi, G., & Caricasole, A. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03867.x · Cited by 101 · see citing works
Apolipoprotein E gene polymorphism and the risk of cardiovascular disease and type 2 diabetes
Liu, S., Liu, J., Weng, R., Gu, X., & Zhong, Z. (2019) · BMC Cardiovascular Disorders · doi:10.1186/s12872-019-1194-0 · Cited by 98 · see citing works
The Alzheimer’s disease risk factors apolipoprotein E and TREM2 are linked in a receptor signaling pathway
Jendresen, C., Årskog, V., Daws, M. R., & Nilsson, L. N. G. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0835-4 · Cited by 94 · see citing works
Association of Rare APOE Missense Variants V236E and R251G With Risk of Alzheimer Disease
Le Guen, Y., Belloy, M. E., Grenier-Boley, B., de Rojas, I., Castillo-Morales, A., Jansen, I., Nicolas, A., Bellenguez, C., Dalmasso, C., Küçükali, F., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2022.1166 · Cited by 93 · see citing works
Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia
Sepulveda-Falla, D., Sanchez, J. S., Almeida, M. C., Boassa, D., Acosta-Uribe, J., Vila-Castelar, C., Ramirez-Gomez, L., Baena, A., Aguillon, D., Villalba-Moreno, N. D., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02467-8 · Cited by 92 · see citing works
Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration
Kuszczyk, M. A., Sanchez, S., Pankiewicz, J., Kim, J., Duszczyk, M., Guridi, M., Asuni, A. A., Sullivan, P. M., Holtzman, D. M., & Sadowski, M. J. (2013) · The American Journal of Pathology · doi:10.1016/j.ajpath.2013.01.034 · Cited by 89 · cited 1× · see citing works
“Peptides binding to residues 12–28 of apoE have been shown to inhibit this interaction [201] and effectively reduce Aβ pathology and synaptic loss in mouse models of AD [202].”
Background
ApoE (Apolipoprotein E) in brain pericytes regulates endothelial function in an isoform-dependent manner by modulating basement membrane components
Yamazaki, Y., Shinohara, M., Yamazaki, A., Ren, Y., Asmann, Y. W., Kanekiyo, T., & Bu, G. (2020) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.119.313169 · Cited by 89 · see citing works
Self-citation
The informed road map to prevention of Alzheimer Disease: a call to arms
McDade, E., Llibre-Guerra, J. J., Holtzman, D. M., Morris, J. C., & Bateman, R. J. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00467-y · Cited by 89 · see citing works
Lipoproteins in the Central Nervous System: From Biology to Pathobiology
Raulin, A.-C., Martens, Y. A., & Bu, G. (2022) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-032620-104801 · Cited by 89 · see citing works
Self-citation
Effect of Domain Interaction on Apolipoprotein E Levels in Mouse Brain
Ramaswamy, G., Xu, Q., Huang, Y., & Weisgraber, K. H. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1922-05.2005 · Cited by 87 · see citing works
Melatonin levels in the Alzheimer’s disease continuum: a systematic review
Nous, A., Engelborghs, S., & Smolders, I. J. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-021-00788-6 · Cited by 87 · see citing works
Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers
Norwitz, N. G., Saif, N., Ariza, I. E., & Isaacson, R. (2021) · Nutrients · doi:10.3390/nu13041362 · Cited by 87 · see citing works
APOΕ4 lowers energy expenditure in females and impairs glucose oxidation by increasing flux through aerobic glycolysis
Farmer, B. C., Williams, H. C., Devanney, N. A., Piron, M. A., Nation, G. K., Carter, D. J., Walsh, A. E., Khanal, R., Young, L. E. A., Kluemper, J. C., et al. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00483-y · Cited by 87 · see citing works
Disturbance in uniformly13C-labelled DHA metabolism in elderly human subjects carrying the apoE ε4 allele
Chouinard‐Watkins, R., Rioux‐Perreault, C., Fortier, M., Tremblay‐Mercier, J., Zhang, Y., Lawrence, P., Vohl, M., Perron, P., Lorrain, D., Brenna, J. T., et al. (2013) · British Journal Of Nutrition · doi:10.1017/s0007114513001268 · Cited by 86 · see citing works

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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.
Zhang, J., Zhang, Y., Wang, J., Xia, Y., Zhang, J., & Chen, L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01911-3 · Cited by 1,138 · see citing works
“Compared to APOE3 and APOE2, APOE4-mediated pathways of A β clearance are impaired, and APOE4 exhibits a higher af ﬁ nity interaction with A β , potentially driving a more severe A β plaque burden, 119,121,123 making it one of the strongest genetic risk factors for AD.”
Background
Cell type‐specific roles of APOE4 in Alzheimer disease
Blumenfeld, J., Yip, O., Kim, M. J., & Huang, Y. (2024) · Nature Reviews Neuroscience · doi:10.1038/s41583-023-00776-9 · Cited by 202 · see citing works
Updates in Alzheimer's disease: from basic research to diagnosis and therapies
Liu, E., Zhang, Y., & Wang, J. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00432-x · Cited by 220 · see citing works
Multifaceted roles of APOE in Alzheimer disease
Jackson, R. J., Hyman, B. T., & Serrano-Pozo, A. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-00988-2 · Cited by 193 · see citing works
The duality of amyloid-β: its role in normal and Alzheimer’s disease states
Azargoonjahromi, A. (2024) · Molecular Brain · doi:10.1186/s13041-024-01118-1 · Cited by 173 · see citing works
Alzheimer's Disease Puzzle: Delving into Pathogenesis Hypotheses
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Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease
Johnson, E. C. B., Bian, S., Haque, R. U., Carter, E. K., Watson, C. M., Gordon, B. A., Ping, L., Duong, D. M., Epstein, M. P., McDade, E., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02476-4 · Cited by 170 · see citing works
Alzheimer’s Disease: Exploring the Landscape of Cognitive Decline
Tenchov, R., Sasso, J. M., & Zhou, Q. A. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.4c00339 · Cited by 170 · see citing works
Cell-autonomous effects of APOE4 in restricting microglial response in brain homeostasis and Alzheimer’s disease
Liu, C.-C., Wang, N., Chen, Y., Inoue, Y., Shue, F., Ren, Y., Wang, M., Qiao, W., Ikezu, T. C., Li, Z., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01640-9 · Cited by 146 · see citing works
Self-citation
Risk factors in developing amyloid related imaging abnormalities (ARIA) and clinical implications
Doran, S. J., & Sawyer, R. P. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1326784 · Cited by 130 · see citing works
Rationale for a Multi-Factorial Approach for the Reversal of Cognitive Decline in Alzheimer’s Disease and MCI: A Review
Rao, R. V., Subramaniam, K. G., Gregory, J., Bredesen, A. L., Coward, C., Okada, S., Kelly, L., & Bredesen, D. E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021659 · Cited by 105 · see citing works
Iron homeostasis imbalance and ferroptosis in brain diseases
Long, H.-N., Zhu, W.-S., Wei, L.-M., & Zhao, J.-G. (2023) · MedComm · doi:10.1002/mco2.298 · Cited by 108 · see citing works
Alzheimer’s disease as type 3 diabetes: understanding the link and implications
Kciuk, M., Kruczkowska, W., Gałęziewska, J., Wanke, K., Kałuzińska-Kołat, Ż., Aleksandrowicz, M., & Kontek, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252211955 · Cited by 98 · see citing works
Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer’s, Parkinson’s, and ALS
Toader, C., Tătaru, C. P., Munteanu, O., Șerban, M., Covache-Busuioc, R.-A., Ciurea, A. V., & Enyedi, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312613 · Cited by 106 · see citing works
The Expanding Burden of Neurodegenerative Diseases: An Unmet Medical and Social Need
Wang, S., Jiang, Y., Yang, A., Meng, F., & Zhang, J. (2024) · Aging and Disease · doi:10.14336/ad.2024.1071 · Cited by 115 · see citing works
The Microbiota–Gut–Brain Axis and Neurological Disorders: A Comprehensive Review
Nakhal, M. M., Yassin, L. K., Alyaqoubi, R., Saeed, S., Alderei, A., Alhammadi, A., Alshehhi, M., Almehairbi, A., Houqani, S. A., BaniYas, S., et al. (2024) · Life · doi:10.3390/life14101234 · Cited by 134 · see citing works
Epigenetic Changes in Alzheimer’s Disease: DNA Methylation and Histone Modification
Plano, L. M. D., Saitta, A., Oddo, S., & Caccamo, A. (2024) · Cells · doi:10.3390/cells13080719 · Cited by 91 · see citing works
Unveiling the future: Advancements in MRI imaging for neurodegenerative disorders
Du, L., Roy, S., Wang, P., Li, Z., Qiu, X., Zhang, Y., Yuan, J., & Guo, B. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102230 · Cited by 80 · see citing works
Cholesterol imbalance and neurotransmission defects in neurodegeneration
Shin, K. C., Moussa, H. Y. A., & Park, Y. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01273-4 · Cited by 81 · see citing works
Peripheral and central neuroimmune mechanisms in Alzheimer’s disease pathogenesis
Zhang, S., Gao, Y., Zhao, Y., Huang, T. Y., Zheng, Q., & Wang, X. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00812-5 · Cited by 78 · see citing works
Lecanemab (Leqembi) is not the right drug for patients with Alzheimer’s disease
Kurkinen, M. T. (2023) · Advances in Clinical and Experimental Medicine · doi:10.17219/acem/171379 · Cited by 77 · see citing works
Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation
Tassone, F., Protic, D. D., Allen, E. G., Archibald, A. D., Baud, A., Brown, T. W., Budimirovic, D. B., Cohen, J., Dufour, B. D., Eiges, R., et al. (2023) · Cells · doi:10.3390/cells12182330 · Cited by 76 · see citing works
Biomarkers and therapeutic strategies targeting microglia in neurodegenerative diseases: current status and future directions
Noh, M., Kwon, H. S., Kwon, M., Nahm, M., Jin, H. K., Bae, J., & Kim, S. H. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00867-4 · Cited by 85 · see citing works
The Brain–Gut Axis, an Important Player in Alzheimer and Parkinson Disease: A Narrative Review
Caradonna, E., Nemni, R., Bifone, A., Gandolfo, P., Costantino, L., Giordano, L., Mormone, E., Macula, A., Cuomo, M., Difruscolo, R., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13144130 · Cited by 75 · see citing works
Neuroprotective Effects of Metformin Through the Modulation of Neuroinflammation and Oxidative Stress
Reed, S., Taka, E., Darling‐Reed, S., & Soliman, K. F. A. (2025) · Cells · doi:10.3390/cells14141064 · Cited by 71 · see citing works
From Genetics to Neuroinflammation: The Impact of ApoE4 on Microglial Function in Alzheimer’s Disease
Dias, D., Portugal, C. C., Relvas, J. B., & Socodato, R. (2025) · Cells · doi:10.3390/cells14040243 · Cited by 66 · see citing works
Gut microbiota-host lipid crosstalk in Alzheimer’s disease: implications for disease progression and therapeutics
Luo, Y., Yang, L.-L., & Yao, X. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00720-0 · Cited by 70 · see citing works
Co-aggregation with Apolipoprotein E modulates the function of Amyloid-β in Alzheimer’s disease
Xia, Z., Prescott, E. E., Urbanek, A., Wareing, H. E., King, M. C., Olerinyova, A., Dakin, H., Leah, T., Barnes, K. A., Matuszyk, M. M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49028-z · Cited by 67 · see citing works
Mitochondria in Alzheimer’s Disease Pathogenesis
Reiss, A. B., Gulkarov, S., Jacob, B., Srivastava, A., Pinkhasov, A., Gomolin, I. H., Stecker, M. M., Wısnıewskı, T., & Leon, J. D. (2024) · Life · doi:10.3390/life14020196 · Cited by 62 · see citing works
The Role of Glial Cell Senescence in Alzheimer's Disease
Alshaebi, F., Sciortino, A., & Kayed, R. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70051 · Cited by 60 · see citing works
Altered ubiquitin signaling induces Alzheimer’s disease-like hallmarks in a three-dimensional human neural cell culture model
Maniv, I., Sarji, M., Bdarneh, A., Feldman, A., Ankawa, R., Koren, E., Magid-Gold, I., Reis, N., Soteriou, D., Salomon‐Zimri, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41545-7 · Cited by 52 · see citing works
Large‐scale deep proteomic analysis in Alzheimer's disease brain regions across race and ethnicity
Seifar, F., Fox, E. J., Shantaraman, A., Liu, Y., Dammer, E. B., Modeste, E., Duong, D. M., Yin, L., Trautwig, A. N., Guo, Q., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.14360 · Cited by 52 · see citing works
Deciphering the mechanisms, biochemistry, physiology, and social habits in the process of aging
Asejeje, F. O., & Ogunro, O. B. (2023) · Archives of Gerontology and Geriatrics Plus · doi:10.1016/j.aggp.2023.100003 · Cited by 54 · see citing works
Amplified fluorogenic immunoassay for early diagnosis and monitoring of Alzheimer’s disease from tear fluid
Lee, S., Kim, E., Moon, C., Park, C., Lim, J.-W., Baek, M. S., Shin, M., Ki, J., Cho, H., Ji, Y. W., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43995-5 · Cited by 49 · see citing works
CRISPR/Cas9 genome editing for neurodegenerative diseases
Nojadeh, J. N., Eryilmaz, N. S. B., & Ergüder, B. İ. (2023) · EXCLI journal · doi:10.17179/excli2023-6155 · Cited by 53 · see citing works
TOMM40 Genetic Variants Cause Neuroinflammation in Alzheimer’s Disease
Chen, Y., Chang, S., Lee, Y., Ho, W.-M., Huang, Y.-H., Wu, Y.-Y., Chu, Y.-C., Wu, K.-H., Wei, L.-S., Wang, H., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24044085 · Cited by 48 · see citing works
Spatial neurolipidomics—MALDI mass spectrometry imaging of lipids in brain pathologies
Jha, D., Blennow, K., Zetterberg, H., Savas, J. N., & Hanrieder, J. (2024) · Journal of Mass Spectrometry · doi:10.1002/jms.5008 · Cited by 47 · see citing works
Early- and Late-Onset Alzheimer’s Disease: Two Sides of the Same Coin?
Valdez-Gaxiola, C. A., Rosales-Leycegui, F., Gaxiola-Rubio, A., Moreno-Ortíz, J. M., & Figuera, L. E. (2024) · Diseases · doi:10.3390/diseases12060110 · Cited by 50 · see citing works
Bridging systemic metabolic dysfunction and Alzheimer’s disease: the liver interface
Song, D., Yang, L., Yang, L.-L., Luo, Y., & Yao, X. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00849-6 · Cited by 53 · see citing works
Potential Implications of miRNAs in the Pathogenesis, Diagnosis, and Therapeutics of Alzheimer’s Disease
Wang, L., Shui, X., Diao, Y., Chen, D., Zhou, Y., & Lee, T. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216259 · Cited by 46 · see citing works
Gut microbiota in Alzheimer’s disease: Understanding molecular pathways and potential therapeutic perspectives
Lista, S., Munafò, A., Caraci, F., Imbimbo, C., Emanuele, E., Minoretti, P., Pinto-Fraga, J., Merino-País, M., Crespo‐Escobar, P., López‐Ortiz, S., et al. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102659 · Cited by 48 · see citing works
Addressing the Discrepancies Between Animal Models and Human Alzheimer’s Disease Pathology: Implications for Translational Research
Polis, B., & Samson, A. O. (2024) · Journal of Alzheimer's Disease · doi:10.3233/jad-240058 · Cited by 43 · see citing works
Astrocyte and oligodendrocyte pathology in Alzheimer's disease
Ziar, R., Tesar, P. J., & Clayton, B. L. L. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00540 · Cited by 47 · see citing works
Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses
Hein, Z. M., Karikalan, B., Gopalakrishna, P. K., Dhevi, K., Alkatiri, A., Hussan, F., Mohd Moklas, M. A., Jagadeesan, S., Che Ramli, M. D., Che Mohd Nassir, C. M. N., et al. (2026) · Molecular Neurobiology · doi:10.1007/s12035-025-05602-0 · Cited by 43 · see citing works
Multiomics analysis to explore blood metabolite biomarkers in an Alzheimer’s Disease Neuroimaging Initiative cohort
Oka, T., Matsuzawa, Y., Tsuneyoshi, M., Nakamura, Y., Aoshima, K., Tsugawa, H., Weiner, M. W., Aisen, P. S. S., Petersen, R. C., Jack, C. R., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-56837-1 · Cited by 42 · see citing works
Multi-target approach to Alzheimer’s disease prevention and treatment: antioxidant, anti-inflammatory, and amyloid- modulating mechanisms
Abbas, K., Mustafa, M., Alam, M., Habib, S., Ahmad, W., Adnan, M., Hassan, M. I., & Usmani, N. (2025) · Neurogenetics · doi:10.1007/s10048-025-00821-y · Cited by 44 · see citing works
AI-powered precision medicine: utilizing genetic risk factor optimization to revolutionize healthcare
Alsaedi, S. B., Ogasawara, M., Alarawi, M. S., Gao, X., & Gojobori, T. (2025) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqaf038 · Cited by 40 · see citing works
The vascular contribution of apolipoprotein E to Alzheimer’s disease
Chen, F., Zhao, J., Meng, F., He, F., Ni, J., & Fu, Y. (2024) · Brain · doi:10.1093/brain/awae156 · Cited by 38 · see citing works
Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives
Liu, Z., Liu, M., Xiong, Y., Wang, Y., & Bu, X. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13864 · Cited by 39 · see citing works
Molecular mechanisms and therapeutic potential of lithium in Alzheimer’s disease: repurposing an old class of drugs
Shen, Y., Zhao, M., Zhao, P., Meng, L., Zhang, Y., Zhang, G., Taishi, Y., & Sun, L. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1408462 · Cited by 43 · see citing works
Multi-functional role of apolipoprotein E in neurodegenerative diseases
Islam, S., Noorani, A., Sun, Y., Michikawa, M., & Zou, K. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1535280 · Cited by 30 · see citing works
Gut microbial metabolites and the brain–gut axis in Alzheimer’s disease: A review
Ji, X., Wang, J., Lan, T., Zhao, D., & Xu, P. (2025) · Biomolecules and Biomedicine · doi:10.17305/bb.2025.12921 · Cited by 37 · see citing works
New insights into methods to measure biological age: a literature review
Mathur, A., Taurin, S., & Alshammary, S. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1395649 · Cited by 37 · see citing works
The brain on time: links between development and neurodegeneration
Shabani, K., & Hassan, B. A. (2023) · Development · doi:10.1242/dev.200397 · Cited by 35 · see citing works
Neuroinflammation is associated with Alzheimer’s disease co-pathology in dementia with Lewy bodies
van Wetering, J., Geut, H., Bol, J. G. J. M., Galis, Y., Timmermans, E., Twisk, J. W. R., Hepp, D. H., Morella, M. L., Pihlstrøm, L., Lemstra, A. W., et al. (2024) · Acta Neuropathologica Communications · doi:10.1186/s40478-024-01786-z · Cited by 36 · see citing works
Plasma phospho-tau217 as a predictive biomarker for Alzheimer’s disease in a large south American cohort
Pandey, N., Yang, Z., Cieza, B., Reyes‐Dumeyer, D., Kang, M. S., Montesinos, R., Soto‐Añari, M., Custodio, N., Honig, L. S., & Tosto, G. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01655-w · Cited by 37 · see citing works
Single‐cell RNA sequencing of retina revealed novel transcriptional landscape in high myopia and underlying cell‐type‐specific mechanisms
Yao, Y., Chen, Z., Wu, Q., Lü, Y., Zhou, X., & Zhu, X. (2023) · MedComm · doi:10.1002/mco2.372 · Cited by 33 · see citing works
Elevated expression of the retrotransposon LINE-1 drives Alzheimer’s disease-associated microglial dysfunction
Roy, N., Haq, I., Ngo, J. C., Bennett, D. A., Teich, A. F., Jager, P. L. D., Olah, M., & Sher, F. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02835-6 · Cited by 35 · see citing works
A small-molecule TLR4 antagonist reduced neuroinflammation in female E4FAD mice
Balu, D., Valencia‐Olvera, A. C., Nguyen, A. Q., Patnam, M., York, J. M., Peri, F., Neumann, F., LaDu, M. J., & Tai, L. M. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01330-6 · Cited by 32 · see citing works
Evaluating the efficacy and safety of Alzheimer’s disease drugs: A meta-analysis and systematic review
Chen, Y., Lai, M., & Tao, M. (2024) · Medicine · doi:10.1097/md.0000000000037799 · Cited by 35 · see citing works
Association Between Type 2 Diabetes Mellitus and Alzheimer's Disease: Common Molecular Mechanism and Therapeutic Targets
Chauhan, A., Dubey, S., & Jain, S. (2024) · Cell Biochemistry and Function · doi:10.1002/cbf.4111 · Cited by 34 · see citing works
Contribution of amyloid deposition from oligodendrocytes in a mouse model of Alzheimer’s disease
Ishii, A., Pathoulas, J., Omar, O. M., Ge, Y., Yao, A. Y., Pantalena, T., Singh, N., Zhou, J., He, W., Murphy, P. A., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00759-z · Cited by 31 · see citing works
A programmable dual-targeting siRNA scaffold supports potent two-gene modulation in the central nervous system
Belgrad, J., Tang, Q., Hildebrand, S. R., Summers, A., Sapp, E., Echeverria, D., O’Reilly, D., Luu, E., Bramato, B. M., Allen, S. E., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae368 · Cited by 31 · see citing works
Magnesium and Cognitive Health in Adults: A Systematic Review and Meta-Analysis
Chen, F., Wang, J., Cheng, Y., Li, R., Wang, Y., Chen, Y., Scott, T. M., & Tucker, K. L. (2024) · Advances in Nutrition · doi:10.1016/j.advnut.2024.100272 · Cited by 31 · see citing works
Navigating the metabolic maze: anomalies in fatty acid and cholesterol processes in Alzheimer’s astrocytes
Zhang, X., Chen, C., & Liu, Y. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01430-x · Cited by 32 · see citing works
Mesoporous Silica Nanoparticles: Types, Synthesis, Role in the Treatment of Alzheimer’s Disease, and Other Applications
Sivamaruthi, B. S., Kapoor, D. U., Kukkar, R. R., Gaur, M., Elossaily, G. M., Prajapati, B. G., & Chaiyasut, C. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15122666 · Cited by 29 · see citing works
Effects of Lipoproteins on Metabolic Health
Albitar, O., D’Souza, C. M., & Adeghate, E. A. (2024) · Nutrients · doi:10.3390/nu16132156 · Cited by 37 · see citing works
Genomic and Transcriptomic Approaches Advance the Diagnosis and Prognosis of Neurodegenerative Diseases
Liu, Z., & Song, S. (2025) · Genes · doi:10.3390/genes16020135 · Cited by 30 · see citing works
The Sigma Receptors in Alzheimer’s Disease: New Potential Targets for Diagnosis and Therapy
Wang, T., & Jia, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512025 · Cited by 29 · see citing works
CRISPRi-based screens in iAssembloids to elucidate neuron-glia interactions
Li, E., Benitez, C., Boggess, S. C., Koontz, M., Rose, I. V. L., Martinez, D., Dräger, N. M., Teter, O. M., Samelson, A. J., Pierce, N., et al. (2025) · Neuron · doi:10.1016/j.neuron.2024.12.016 · Cited by 35 · see citing works
Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies
Sekiya, H., Matsubara, T., Deture, M. A., & Dickson, D. W. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00900-6 · Cited by 30 · see citing works
The future is precision medicine-guided diagnoses, preventions and treatments for neurodegenerative diseases
Rossi, S. L., Subramanian, P., & Bovenkamp, D. E. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1128619 · Cited by 28 · see citing works
Alzheimer's Disease: A Review of Pathology, Current Treatments, and the Potential Therapeutic Effect of Decreasing Oxidative Stress by Combined Vitamin D and l -Cysteine Supplementation
Jain, S. K., Stevens, C. M., Margret, J. J., & Levine, S. N. (2023) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0245 · Cited by 27 · see citing works
Alzheimer’s Disease Etiology Hypotheses and Therapeutic Strategies: A Perspective
Scarano, N., Musumeci, F., Casini, B., Brullo, C., D’Ursi, P., Fossa, P., Schenone, S., & Cichero, E. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26146980 · Cited by 30 · see citing works
Drugs targeting APOE4 that regulate beta‐amyloid aggregation in the brain: Therapeutic potential for Alzheimer's disease
Poblano, J., Castillo‐Tobías, I., Berlanga, L., Tamayo‐Ordoñez, M. C., Rodríguez‐Salazar, M. D. C., Silva‐Belmares, S. Y., Aguayo‐Morales, H., & Cobos-Puc, L. E. (2024) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.14055 · Cited by 27 · see citing works
Advances in Alzheimer's therapy: Exploring neuropathological mechanisms to revolutionize the future therapeutic landscape
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Self-citation

Authors: Raulin, A.-C., Doss, S. V., Trottier, Z. A., Ikezu, T. C., Bu, G., & Liu, C.-C.
Affiliations: Mayo Clinic in Florida (US)
Corresponding author: Bu, Guojun
Liu, Chia-Chen
ORCID: Raulin, Ana-Caroline
Doss, Sydney V.
Trottier, Zachary A.
Ikezu, Tadafumi C.
Bu, Guojun
Liu, Chia-Chen
Venue: Molecular Neurodegeneration
Publisher: Springer Science and Business Media LLC
Published: 2022-11-08
Volume: 17
Issue: 1
Pages: 72-72
ISSN: 1750-1326 (ISSN-L)
DOI: 10.1186/s13024-022-00574-4
PMC: PMC9644639
OpenAlex: W4308572221
Cited by: 756
References: 317
Citations by year: 2026: 222 · 2025: 266 · 2024: 187 · 2023: 81
FWCI: 18.38
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Molecular Neurodegeneration (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders: NIH Blueprint for Neuroscience Research (R37AG027924, RF1AG057181, U19AG069701, U19AG069701, R01AG062110)
Cure Alzheimer’s Fund (Cure Alzheimer’s Fund)
Topics: Health Sciences › Medicine › Physiology › 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, Alzheimer's disease, APOE ε4, APOE isoforms, amyloid plaques, lipid transport, genetic risk factors
MeSH terms: Alleles, Alzheimer Disease, Apolipoproteins E, Humans, Amyloid beta-Peptides, Apolipoprotein E4, Plaque, Amyloid

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