Apolipoprotein E: Structure and function in lipid metabolism, neurobiology, and Alzheimer’s diseases
Open accessAbstract
Apolipoprotein (apo) E is a multifunctional protein with central roles in lipid metabolism, neurobiology, and neurodegenerative diseases. It has three major isoforms (apoE2, apoE3, and apoE4) with different effects on lipid and neuronal homeostasis. A major function of apoE is to mediate the binding of lipoproteins or lipid complexes in the plasma or interstitial fluids to specific cell-surface receptors. These receptors internalize apoE-containing lipoprotein particles; thus, apoE participates in the distribution/redistribution of lipids among various tissues and cells of the body. In addition, intracellular apoE may modulate various cellular processes physiologically or pathophysiologically, including cytoskeletal assembly and stability, mitochondrial integrity and function, and dendritic morphology and function. Elucidation of the functional domains within this protein and of the three-dimensional structure of the major isoforms of apoE has contributed significantly to our understanding of its physiological and pathophysiological roles at a molecular level. It is likely that apoE, with its multiple cellular origins and multiple structural and biophysical properties, is involved widely in processes of lipid metabolism and neurobiology, possibly encompassing a variety of disorders of neuronal repair, remodeling, and degeneration by interacting with different factors through various pathways.
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
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?
ApoE4 is excessively produced by damaged neurons.
“elegant research from Mahley’s laboratory demonstrated in Neuro-2a neuronal cells expressing stable isoforms of apolipoprotein E (apoE), i.e., apoE2, apoE3, or apoE4, with the latter a major risk factor for developing AD, that apoE4 is excessively produced by damaged neurons [31].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [31]
In “Synthesis of ApoE in Different Tissues and Cells” (page unavailable), the review reports that hippocampal and cortical neurons express apoE in response to injury. In “ApoE4 proteolysis and neurotoxicity” (page unavailable), it hypothesizes that injury enhances neuronal apoE expression, but does not establish that damaged neurons excessively produce apoE4 specifically. Its discussion of apoE-transfected Neuro-2a cells concerns neurite extension, not production by damaged neurons. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn apoE4 neurons, mitochondrial respiration and glycolysis are negatively affected under basal conditions, and stressed or damaged apoE4 neurons have half the ATP reserve capacity of apoE3 neurons.
“For the latter, mitochondrial respiration (as well as glycolysis) was negatively affected under basal conditions, but if stressed or damaged, apoE4 neurons had half the ATP reserve capacity of apoE3 neurons.”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [31]
The section “ApoE4 fragments disrupt cytoskeletal structure and impair mitochondrial function” (page unavailable) reports mitochondrial dysfunction in neurons and decreased cerebral glucose metabolism associated with apoE4. It does not establish impaired neuronal respiration and glycolysis under basal conditions or the claim that stressed apoE4 neurons have half the ATP reserve capacity of apoE3 neurons; searches for those terms found no supporting passage. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn the periphery, ApoE has important implications in atherosclerosis and hyperlipoproteinemia, which also affect cerebral vasculature.
“In the periphery, ApoE has important implications in atherosclerosis and hyperlipoproteinemia [3,23], which also affect cerebral vasculature.”
From Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease (2017) · cites this paper as [3]
The Introduction and Receptor and Heparan Sulfate Proteoglycan Binding Activity section describe ApoE’s role in plasma lipoprotein clearance and link ApoE variants to type III hyperlipoproteinemia. The paper does not substantiate the cited clause’s claim about atherosclerosis; its discussion of blood–brain barrier integrity does not link either peripheral condition to effects on cerebral vasculature. No page numbers are available in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredAPOE has diverse roles in numerous biological processes including lipid metabolism, immunity, mitochondrial function, and neuronal repair.
“This is a product of the pronounced complexity of APOE, which has diverse roles in numerous biological processes including lipid metabolism, immunity, mitochondrial function, and neuronal repair (7,37).”
From Apolipoprotein E2 Stimulates Protein Synthesis and Promotes Melanoma Progression and Metastasis (2023) · cites this paper as [37]
The Introduction describes apoE’s role in lipid transport, and the neurobiology section links it to peripheral nerve repair. The paper also describes effects on mitochondrial function. It reports apoE production by macrophages and an apoE4-linked proinflammatory pathway, but does not clearly establish the broader claimed role in immunity. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe ApoE-lipoprotein complex has been shown to alter the lipid profile of cancer and noncancerous cells.
“The ApoE-lipoprotein complex has been shown to alter the lipid profile of cancer and noncancerous cells (47–49).”
From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [48]
The Introduction and “Structure and Function of ApoE Isoforms in Lipid Metabolism” sections (page numbers unavailable) say that apoE-containing lipoproteins transport lipids among cells and help regulate tissue lipid content. They do not report a demonstrated change in the lipid profiles of both cancer and noncancerous cells; the mention of neuroblastoma cells concerns neurite outgrowth, not their lipid profile. (LLM, conf=0.83)
Experimental — accuracy not yet measured
The strongest protective allele against LOAD, APOEε2, has the lowest frequency of the three alleles at the APOE locus.
“In fact, the strongest protective allele against LOAD, APOEε2, has the lowest frequency of the three alleles at the APOE locus75.”
From Variant-to-function mapping of late-onset Alzheimer’s disease GWAS signals in human microglial cell models implicates <i>RTFDC1</i> at the <i>CASS4</i> locus (2024) · cites this paper as [75]
The Introduction (page unavailable) identifies apoE3 as the most common of the three isoforms, but does not establish whether apoE2 is less frequent than apoE4. The Aβ-dependent effects section reports that apoE2 and apoE3 cleared more Aβ than apoE4 in transgenic mice; it does not establish that APOEε2 is the strongest protective allele against late-onset Alzheimer’s disease. (LLM, conf=0.76)
Experimental — accuracy not yet measuredApoE4 fragments are neurotoxic and negatively affect tau biology and mitochondrial function.
“The resulting apoE4 fragments were demonstrated by the Mahley laboratory to be neurotoxic, specifically negatively affecting tau biology and mitochondrial function [31].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [31]
In plasma, ApoE4 associates preferentially with large, triglyceride-rich VLDL particles while ApoE2 and ApoE3 have a preference for small, phospholipid-rich HDL.
“In the plasma, ApoE4 associates preferentially with large, triglyceride-rich VLDL particles while ApoE2 and ApoE3 have a preference for small, phospholipid-rich HDL [3].”
From Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease (2017) · cites this paper as [3]
ApoE plays a key role in lipid metabolism in the brain via ApoE receptor-mediated uptake of lipoprotein particles.
“ApoE plays a key role in the lipid metabolism in the brain via ApoE receptor-mediated uptake of lipoprotein particles [3].”
From Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease (2017) · cites this paper as [3]
APOE4 is the strongest genetic risk factor for late-onset Alzheimer's disease.
“Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD)1–3.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [3]
ApoE is a key constituent of plasma LNPs although the secreted apoprotein is undetectable in plasma.
“apolipoprotein E (ApoE) is a key constituent of plasma LNPs7, 8 although the secreted apoprotein is undetectable in plasma.9, 10”
From ApoE is Secreted as a Lipid Nanoparticle by Mammalian Cells: Implications for Alzheimer’s Disease Pathogenesis (2025) · cites this paper as [7]
APOE plays a central role in neuronal lipid homeostasis, membrane remodeling, and neurite dynamics in an isoform dependent manner, with protective variants supporting greater structural resilience and synaptic integrity.
“APOE plays a central role in neuronal lipid homeostasis, membrane remodeling, and neurite dynamics in an isoform dependent manner, with protective variants supporting greater structural resilience and synaptic integrity (Huang and Mahley, 2014; Lindner et al., 2024).”
From APOE3-Christchurch variant enhances neurovascular support functions of iPSC-derived mesenchymal stromal cells (2026) · cites this paper as Huang and Mahley, 2014
ApoE, mainly a plasma lipoprotein component, can also exist in non-lipidated form and within EVs.
“ApoE, mainly a plasma lipoprotein component, 55 can also exist in non‐lipidated form and within EVs. 56 , 57”
In the central nervous system, apoE is mainly secreted by astrocytes, with different isoforms playing distinct roles in lipid metabolism and nervous system homeostasis.
“In the central nervous system (CNS), apoE is mainly secreted by astrocytes, with different isoforms playing distinct roles in lipid metabolism and nervous system homeostasis [11, 12].”
From APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline (2021) · cites this paper as [11]
Changes in apoE4 neurons correlate with proteomics-identified altered levels of proteins associated with mitochondrial fission/fusion dynamics.
“These changes were correlated to proteomics-identified altered levels of proteins associated with mitochondrial fission/fusion dynamics among other mitochondrial proteins [31].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [31]
The section “ApoE4 fragments disrupt cytoskeletal structure and impair mitochondrial function” reports mitochondrial dysfunction and reduced mitochondrial mobility in neurons, but not a correlation with altered protein levels. Searches for proteomics and mitochondrial fission/fusion found no passage addressing the claimed protein changes; page numbers were unavailable in our copy. (LLM, conf=0.75)
Experimental — accuracy not yet measuredApoE4 neurons show a lower NAD+/NADH ratio and elevated ROS and mitochondrial Ca2+.
“A lower NAD+/NADH ratio and elevated ROS and mitochondrial Ca2+ also were observed.”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [31]
The section “ApoE4 fragments disrupt cytoskeletal structure and impair mitochondrial function” (page unavailable) describes mitochondrial dysfunction in neurons but does not report the claimed measurements. Searches for NADH, ROS, and mitochondrial Ca2+ found no passage establishing a lower NAD+/NADH ratio or elevated ROS or mitochondrial Ca2+ in ApoE4 neurons. (LLM, conf=0.72)
Experimental — accuracy not yet measuredApolipoprotein E4 is the major genetic risk factor for late-onset familial and sporadic Alzheimer's disease.
“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 [8]
ApoE4 increases the risk and decreases the age of onset of Alzheimer's disease in a gene dose dependent manner.
“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 [8]
The apoE3 and apoE4 amino acid sequences differ only at position 112, where apoE4 has an arginine instead of a cysteine.
“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 [8]
ApoE plays major roles in Alzheimer's disease pathogenesis in both an amyloid-β-dependent and independent manner.
“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 [8]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The metabolic and molecular bases of inherited disease
Chen, Y.-T. (2001) · Medical Entomology and Zoology · Cited by 6,928 · see citing works
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268 · see citing works
Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology
Mahley, R. W. (1988) · Science · doi:10.1126/science.3283935 · Cited by 4,028 · see citing works
Self-citationCellular uptake of the tat protein from human immunodeficiency virus
Frankel, A. D., & Pabo, C. O. (1988) · Cell · doi:10.1016/0092-8674(88)90263-2 · Cited by 2,782 · see citing works
Alzheimer Mechanisms and Therapeutic Strategies
Huang, Y., & Mucke, L. (2012) · Cell · doi:10.1016/j.cell.2012.02.040 · Cited by 1,758 · see citing works
Self-citationThe role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · see citing works
Distinct patterns of brain activity in young carriers of the <i>APOE</i> -ε4 allele
Filippini, N., MacIntosh, B. J., Hough, M. G., Goodwin, G. M., Frisoni, G. B., Smith, S. M., Matthews, P. M., Beckmann, C. F., & Mackay, C. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811879106 · Cited by 1,613 · see citing works
Green, M., & Loewenstein, P. M. (1988) · Cell · doi:10.1016/0092-8674(88)90262-0 · Cited by 1,551 · see citing works
Mitochondrial abnormalities in Alzheimer's disease
Hirai, K., Aliev, G., Nunomura, A., Fujioka, H., Russell, R. L., Atwood, C. S., Johnson, A. B., Kress, Y., Vinters, H. V., Tabaton, M., et al. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-09-03017.2001 · Cited by 1,367 · see citing works
Strittmatter, W. J., Weisgraber, K. H., Huang, D. Y., Dong, L. M., Salvesen, G. S., Pericak-Vance, M., Schmechel, D., Saunders, A. M., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.8098 · Cited by 1,363 · see citing works
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A
Bell, R. D., Winkler, E. A., Singh, I., Sagare, A. P., Deane, R., Wu, Z., Holtzman, D. M., Betsholtz, C., Armulik, A., Sallstrom, J., et al. (2012) · Nature · doi:10.1038/nature11087 · Cited by 1,293 · see citing works
Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance
Castellano, J. M., Kim, J., Stewart, F. R., Jiang, H., DeMattos, R. B., Patterson, B. W., Fagan, A. M., Morris, J. C., Mawuenyega, K. G., Cruchaga, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002156 · Cited by 1,227 · see citing works
Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy
Bu, G. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2620 · Cited by 1,168 · see citing works
Namba, Y., Tomonaga, M., Kawasaki, H., Otomo, E., & Ikeda, K. (1991) · Brain Research · doi:10.1016/0006-8993(91)91092-f · Cited by 1,157 · see citing works
ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models
Cramer, P. E., Cirrito, J. R., Wesson, D. W., Lee, C. Y. D., Karlo, J. C., Zinn, A. E., Casali, B. T., Restivo, J. L., Goebel, W. D., James, M. J., et al. (2012) · Science · doi:10.1126/science.1217697 · Cited by 1,050 · see citing works
Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia
Reiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D., Saunders, A. M., & Hardy, J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2635903100 · Cited by 977 · see citing works
Holtzman, D. M., Bales, K. R., Tenkova, T., Fagan, A. M., Parsadanian, M., Sartorius, L. J., Mackey, B., Olney, J., McKeel, D., Wozniak, D., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.050004797 · Cited by 937 · see citing works
Mahley, R. W., Weisgraber, K. H., & Huang, Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600549103 · Cited by 912 · see citing works
Self-citationDavies, P., Katzman, R., & Terry, R. D. (1980) · Nature · doi:10.1038/288279a0 · Cited by 882 · see citing works
Apolipoprotein E: Structure-Function Relationships
Weisgraber, K. H. (1994) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60642-7 · Cited by 830 · see citing works
Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid
Wisniewski, T., & Frangione, B. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90444-c · Cited by 802 · see citing works
Differential Effects of Apolipoproteins E3 and E4 on Neuronal Growth in Vitro
Nathan, B. P., Bellosta, S., Sanan, D. A., Weisgraber, K. H., Mahley, R. W., & Pitas, R. E. (1994) · Science · doi:10.1126/science.8171342 · Cited by 795 · see citing works
Self-citationapoE isoform–specific disruption of amyloid β peptide clearance from mouse brain
Deane, R., Sagare, A., Hamm, K., Parisi, M., Lane, S., Finn, M. B., Holtzman, D. M., & Zlokovic, B. V. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36663 · Cited by 771 · see citing works
APOLIPOPROTEIN E ALLELES AS RISK FACTORS IN ALZHEIMER'S DISEASE
Roses, M. D. (1996) · Annual Review of Medicine · doi:10.1146/annurev.med.47.1.387 · Cited by 707 · see citing works
Mahley, R. W., & Ji, Z.-S. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)33334-4 · Cited by 693 · see citing works
Self-citationAssociation of apolipoprotein E polymorphism with outcome after head injury
Teasdale, G. M., Nicoll, J. A. R., Murray, G. D., & Fiddes, M. (1997) · The Lancet · doi:10.1016/s0140-6736(97)04318-3 · Cited by 683 · see citing works
Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides
Koistinaho, M., Lin, S., Wu, X., Esterman, M., Koger, D., Hanson, J., Higgs, R., Liu, F., Malkani, S., Bales, K. R., et al. (2004) · Nature Medicine · doi:10.1038/nm1058 · Cited by 571 · see citing works
Verghese, P. B., Castellano, J. M., Garai, K., Wang, Y., Jiang, H., Shah, A., Bu, G., Frieden, C., & Holtzman, D. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220484110 · Cited by 556 · see citing works
Clearing the brain's amyloid cobwebs
Selkoe, D. J. (2001) · Neuron · doi:10.1016/s0896-6273(01)00475-5 · Cited by 541 · see citing works
Isoform-specific binding of apolipoprotein E to beta-amyloid.
LaDu, M. J., Falduto, M. T., Manelli, A. M., Reardon, C. A., Getz, G. S., & Frail, D. E. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31529-6 · Cited by 540 · see citing works
Xu, Q., Bernardo, A., Walker, D., Kanegawa, T., Mahley, R. W., & Huang, Y. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.5476-05.2006 · Cited by 524 · see citing works
Self-citationBales, K. R., Verina, T., Cummins, D. J., Du, Y., Dodel, R. C., Saura, J., Fishman, C. E., DeLong, C. A., Piccardo, P., Petegnief, V., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.15233 · Cited by 486 · see citing works
Strittmatter, W. J., Saunders, A. M., Goedert, M., Weisgraber, K. H., Dong, L. M., Jakes, R., Huang, D. Y., Pericak-Vance, M., Schmechel, D., & Roses, A. D. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.11183 · Cited by 474 · see citing works
Wahrle, S. E., Jiang, H., Parsadanian, M., Legleiter, J., Han, X., Fryer, J. D., Kowalewski, T., & Holtzman, D. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407963200 · Cited by 474 · see citing works
Lipoprotein receptors in the nervous system
Herz, J., & Bock, H. H. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.110601.135342 · Cited by 457 · see citing works
Mahley, R. W., Huang, Y., & Rall, S. C. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32417-2 · Cited by 447 · see citing works
Self-citationMayeux, R., Ottman, R., Maestre, G., Ngai, C., Tang, M.-X., Ginsberg, H., Chun, M., Tycko, B., & Shelanski, M. (1995) · Neurology · doi:10.1212/wnl.45.3.555 · Cited by 443 · see citing works
Apolipoprotein E-ε4 genotype predicts a poor outcome in survivors of traumatic brain injury
Friedman, G., Froom, P., Sazbon, L., Grinblatt, I., Shochina, M., Tsenter, J., Babaey, S., Yehuda, A. B., & Groswasser, Z. (1999) · Neurology · doi:10.1212/wnl.52.2.244 · Cited by 437 · see citing works
Strittmatter, W. J., Weisgraber, K. H., Goedert, M., Saunders, A. M., Huang, D., Corder, E. H., Dong, L., Jakes, R., Alberts, M. J., Gilbert, J. R., et al. (1994) · Experimental Neurology · doi:10.1006/exnr.1994.1019 · Cited by 433 · see citing works
Apolipoprotein e sets the stage: response to injury triggers neuropathology
Mahley, R. W., & Huang, Y. (2012) · Neuron · doi:10.1016/j.neuron.2012.11.020 · Cited by 412 · see citing works
Self-citationBrecht, W. J., Harris, F. M., Chang, S., Tesseur, I., Yu, G.-Q., Xu, Q., Dee Fish, J., Wyss-Coray, T., Buttini, M., Mucke, L., et al. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4315-03.2004 · Cited by 403 · see citing works
Self-citationReiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D., Saunders, A. M., & Hardy, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500579102 · Cited by 401 · see citing works
Huang, Y., Liu, X. Q., Wyss-Coray, T., Brecht, W. J., Sanan, D. A., & Mahley, R. W. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151254698 · Cited by 392 · see citing works
Self-citationMahley, R. W., & Huang, Y. (1999) · Current Opinion in Lipidology · doi:10.1097/00041433-199906000-00003 · Cited by 388 · see citing works
Self-citationDeficiency of ABCA1 Impairs Apolipoprotein E Metabolism in Brain
Hirsch-Reinshagen, V., Zhou, S., Burgess, B. L., Bernier, L., McIsaac, S. A., Chan, J. Y., Tansley, G. H., Cohn, J. S., Hayden, M. R., & Wellington, C. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407962200 · Cited by 385 · see citing works
GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer’s Disease
Cruchaga, C., Kauwe, J. S. K., Harari, O., Jin, S. C., Cai, Y., Karch, C. M., Benitez, B. A., Jeng, A. T., Skorupa, T., Carrell, D., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.026 · Cited by 383 · see citing works
Chen, Y., Durakoglugil, M. S., Xian, X., & Herz, J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914984107 · Cited by 368 · see citing works
Raber, J., Wong, D., Buttini, M., Orth, M., Bellosta, S., Pitas, R. E., Mahley, R. W., & Mucke, L. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.18.10914 · Cited by 364 · see citing works
Self-citationButtini, M., Orth, M., Bellosta, S., Akeefe, H., Pitas, R. E., Wyss‐Coray, T., Mucke, L., & Mahley, R. W. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-12-04867.1999 · Cited by 355 · see citing works
Self-citationLack of ABCA1 Considerably Decreases Brain ApoE Level and Increases Amyloid Deposition in APP23 Mice
Koldamova, R., Staufenbiel, M., & Lefterov, I. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504513200 · Cited by 350 · see citing works
Holtzman, D. M., Pitas, R. E., Kilbridge, J., Nathan, B., Mahley, R. W., Bu, G., & Schwartz, A. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.21.9480 · Cited by 349 · see citing works
Self-citationMCI conversion to dementia and the APOE genotype
Mosconi, L., Perani, D., Sorbi, S., Herholz, K., Nacmias, B., Holthoff‐Detto, V., Salmon, É., Baron, J., Cristofaro, M. T. D., Padovani, A., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000147469.18313.3b · Cited by 344 · see citing works
Harris, F. M., Brecht, W. J., Xu, Q., Tesseur, I., Kekonius, L., Wyss-Coray, T., Fish, J. D., Masliah, E., Hopkins, P. C., Scearce-Levie, K., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1434398100 · Cited by 342 · see citing works
Self-citationCholesterol in Alzheimer's disease
Shobab, L. A., Hsiung, G. R., & Feldman, H. (2005) · The Lancet Neurology · doi:10.1016/s1474-4422(05)70248-9 · Cited by 332 · see citing works
Andrews-Zwilling, Y., Bien-Ly, N., Xu, Q., Li, G., Bernardo, A., Yoon, S. Y., Zwilling, D., Yan, T. X., Chen, L., & Huang, Y. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4040-10.2010 · Cited by 326 · see citing works
Self-citationDeletion of Abca1 Increases Aβ Deposition in the PDAPP Transgenic Mouse Model of Alzheimer Disease
Wahrle, S. E., Jiang, H., Parsadanian, M., Hartman, R. E., Bales, K. R., Paul, S. M., & Holtzman, D. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508780200 · Cited by 325 · see citing works
Chang, S., Ma, T. R., Miranda, R. D., Balestra, M. E., Mahley, R. W., & Huang, Y. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508254102 · Cited by 319 · see citing works
Self-citationApolipoprotein E epsilon4 and the risk of dementia with stroke. A population-based investigation
Slooter, A. J. C. (1997) · JAMA · doi:10.1001/jama.277.10.818 · Cited by 317 · see citing works
Bellosta, S., Nathan, B. P., Orth, M., Dong, L.-M., Mahley, R. W., & Pitas, R. E. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.45.27063 · Cited by 313 · see citing works
Self-citationLi, G., Bien-Ly, N., Andrews-Zwilling, Y., Xu, Q., Bernardo, A., Ring, K., Halabisky, B., Deng, C., Mahley, R. W., & Huang, Y. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2009.10.015 · Cited by 288 · see citing works
Self-citationApoE genotype and survival from intracerebral haemorrhage
Alberts, M., Graffagnino, C., McClenny, C., DeLong, D. M., Strittmatter, W. J., Saunders, A. M., & Roses, A. D. (1995) · The Lancet · doi:10.1016/s0140-6736(95)91411-0 · Cited by 287 · see citing works
Small, S. A., Chawla, M. K., Buonocore, M. H., Rapp, P. R., & Barnes, C. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400285101 · Cited by 281 · see citing works
Nathan, B. P., Chang, K.-C., Bellosta, S., Brisch, E., Ge, N., Mahley, R. W., & Pitas, R. E. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.34.19791 · Cited by 276 · see citing works
Self-citationCholesterol and the Biology of Alzheimer's Disease
Wolozin, B. (2004) · Neuron · doi:10.1016/s0896-6273(03)00840-7 · Cited by 275 · see citing works
APOE genotype as a risk factor for ischemic cerebrovascular disease
McCarron, M. O., DeLong, D. M., & Alberts, M. J. (1999) · Neurology · doi:10.1212/wnl.53.6.1308 · Cited by 267 · see citing works
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
Self-citationTesseur, I. C., Dorpe, J. V., Spittaels, K., den Haute, C. V., Moechars, D., & LEUVEN, F. V. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64963-2 · Cited by 239 · see citing works
Apolipoprotein E and cognitive performance
Raber, J., Wong, D., Yu, G.-Q., Buttini, M., Mahley, R. W., Pitas, R. E., & Mucke, L. (2000) · Nature · doi:10.1038/35006165 · Cited by 237 · see citing works
Self-citationHirsch-Reinshagen, V., Maia, L. F., Burgess, B. L., Blain, J.-F., Naus, K. E., McIsaac, S. A., Parkinson, P. F., Chan, J. Y., Tansley, G. H., Hayden, M. R., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508781200 · Cited by 233 · see citing works
Fagan, A. M., Bu, G., Sun, Y., Daugherty, A., & Holtzman, D. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.47.30121 · Cited by 226 · see citing works
Fagan, A. M., Holtzman, D. M., Munson, G., Mathur, T., Schneider, D., Chang, L. K., Getz, G. S., Reardon, C. A., Lukens, J., Shah, J. A., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.42.30001 · Cited by 222 · see citing works
ApoE4 Decreases Spine Density and Dendritic Complexity in Cortical Neurons<i>In Vivo</i>
Dumanis, S. B., Tesoriero, J. A., Babus, L. W., Nguyen, M. T., Trotter, J. H., Ladu, M. J., Weeber, E. J., Turner, R. S., Xu, B., Rebeck, G. W., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4026-09.2009 · Cited by 220 · see citing works
Apolipoprotein E receptors: linking brain development and alzheimer's disease
Herz, J., & Beffert, U. (2000) · Nature reviews. Neuroscience · doi:10.1038/35036221 · Cited by 218 · see citing works
Sun, Y., Wu, S., Bu, G., Onifade, M. K., Patel, S. N., LaDu, M. J., Fagan, A. M., & Holtzman, D. M. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-09-03261.1998 · Cited by 213 · see citing works
Exercise improves cognition and hippocampal plasticity in <i>APOE</i> ɛ4 mice
Nichol, K., Deeny, S. P., Seif, J., Camaclang, K., & Cotman, C. W. (2009) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2009.02.006 · Cited by 213 · see citing works
Papassotiropoulos, A., Streffer, J. R., Tsolaki, M., Schmid, S., Thal, D. R., Nicosia, F. M., Iakovidou, V., Maddalena, A. S., Lütjohann, D., Ghebremedhin, E., et al. (2003) · Archives of Neurology · doi:10.1001/archneur.60.1.29 · Cited by 208 · see citing works
Dodart, J.-C., Marr, R. A., Koistinaho, M., Gregersen, B. M., Malkani, S., Verma, I. M., & Paul, S. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409072102 · Cited by 207 · see citing works
APOE genotype influences acquisition and recall following traumatic brain injury
Crawford, F., Vanderploeg, R. D., Freeman, M. J., Singh, S., Waisman, M., Michaels, L., Abdullah, L. I., Warden, D. L., Lipsky, R. H., Salazar, A., et al. (2002) · Neurology · doi:10.1212/wnl.58.7.1115 · Cited by 207 · see citing works
Temporal lobe functional activity and connectivity in young adult <i>APOE</i> ɛ4 carriers
Dennis, N. A., Browndyke, J. N., Stokes, J., Need, A., Burke, J. R., Welsh‐Bohmer, K. A., & Cabeza, R. (2010) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2009.07.003 · Cited by 201 · see citing works
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 · see citing works
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
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
Apolipoprotein E ε4 is associated with rapid progression of multiple sclerosis
Fazekas, F., Strasser‐Fuchs, S., Kollegger, H., Berger, T., Kristoferitsch, W., Schmidt, H., Enzinger, C., Schiefermeier, M., Schwarz, C., Kornek, B., et al. (2001) · Neurology · doi:10.1212/wnl.57.5.853 · Cited by 185 · see citing works
Buttini, M., Yu, G.-Q., Shockley, K., Huang, Y., Jones, B., Masliah, E., Mallory, M., Yeo, T., Longo, F. M., & Mucke, L. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-24-10539.2002 · Cited by 183 · see citing works
APOE genotype is a major predictor of long-term progression of disability in MS
Chapman, J., Vinokurov, S., Achiron, A., Karussis, D. M., Mitosek‐Szewczyk, K., Birnbaum, M., Michaelson, D. M., & Korczyn, A. D. (2001) · Neurology · doi:10.1212/wnl.56.3.312 · Cited by 179 · see citing works
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
Small, S. A. (2001) · Archives of Neurology · doi:10.1001/archneur.58.3.360 · Cited by 174 · see citing works
Kamino, K., Nagasaka, K., Imagawa, M., Yamamoto, H., Yoneda, H., Ueki, A., Kitamura, S., Namekata, K., Miki, T., & Ohta, S. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2923 · Cited by 173 · see citing works
Aβ-independent roles of apolipoprotein E4 in the pathogenesis of Alzheimer's disease
Huang, Y. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.04.004 · Cited by 170 · see citing works
Self-citationBien-Ly, N., Gillespie, A. K., Walker, D., Yoon, S. Y., & Huang, Y. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0033-12.2012 · Cited by 170 · see citing works
Self-citationSadowski, 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
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
Self-citationMahley, R. W., & Huang, Y. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30889 · Cited by 159 · see citing works
Self-citationHartman, R. E., Wozniak, D. F., Nardi, A., Olney, J. W., Sartorius, L., & Holtzman, D. M. (2001) · Experimental Neurology · doi:10.1006/exnr.2001.7715 · Cited by 157 · see citing works
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
Self-citationFitz, N. F., Cronican, A. A., Lefterov, I., & Koldamova, R. (2013) · Science · doi:10.1126/science.1235809 · Cited by 151 · see citing works
Tesseur, I. C., Dorpe, J. V., Bruynseels, K., Bronfman, F. C., Sciot, R., Lommel, A. V., & LEUVEN, F. V. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64788-8 · Cited by 141 · see citing works
Six-month recovery from mild to moderate Traumatic Brain Injury: the role of APOE- 4 allele
Chamelian, L. (2004) · Brain · doi:10.1093/brain/awh296 · Cited by 140 · see citing works
Polymorphism in the cholesterol 24S-hydroxylase gene is associated with Alzheimer's disease
Kölsch, H., Lütjohann, D., Ludwig, M. Z., Schulte, A., Ptok, U., Jessen, F., von Bergmann, K., Rao, M. L., Maier, W., & Heun, R. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001109 · Cited by 139 · see citing works
Price, A. R., Xu, G., Siemienski, Z. B., Smithson, L. A., Borchelt, D. R., Golde, T. E., & Felsenstein, K. M. (2013) · Science · doi:10.1126/science.1234089 · Cited by 138 · see citing works
Fitz, N. F., Cronican, A. A., Saleem, M., Fauq, A. H., Chapman, R., Lefterov, I. M., & Koldamova, R. P. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1937-12.2012 · Cited by 138 · see citing works
Reversal of apoE4-driven brain pathology and behavioral deficits by bexarotene
Boehm-Cagan, A., & Michaelson, D. M. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.5198-13.2014 · Cited by 134 · see citing works
Veeraraghavalu, K., Zhang, C., Miller, S., Hefendehl, J. K., Rajapaksha, T. W., Ulrich, J., Jucker, M., Holtzman, D. M., Tanzi, R. E., Vassar, R., et al. (2013) · Science · doi:10.1126/science.1235505 · Cited by 133 · see citing works
Mahley, R. W., & Huang, Y. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm3008618 · Cited by 132 · see citing works
Self-citationKatzov, H., Chalmers, K. A., Palmgren, J., Andreasen, N., Johansson, B. E. A., Cairns, N. J., Gatz, M., Wilcock, G. K., Love, S., Pedersen, N. L., et al. (2004) · Human Mutation · doi:10.1002/humu.20012 · Cited by 128 · see citing works
Tesseur, I., Lo, A. C., Roberfroid, A., Dietvorst, S., Van Broeck, B., Borgers, M., Gijsen, H., Moechars, D., Mercken, M., Kemp, J., et al. (2013) · Science · doi:10.1126/science.1233937 · Cited by 128 · see citing works
DeMattos, R. B., Curtiss, L. K., & Williams, D. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.7.4206 · Cited by 123 · see citing works
Apolipoprotein E controls the risk and age at onset of Parkinson disease
Li, Y. J., Hauser, M. A., Scott, W. K., Martin, E. R., Booze, M. W., Qin, X. J., Walter, J. W., Nance, M. A., Hubble, J. P., Koller, W. C., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000128089.53030.ac · Cited by 118 · see citing works
Cerebral glucose metabolism in patients with AD and different <i>APOE</i> genotypes
Drzezga, A., Riemenschneider, M., Strassner, B., Grimmer, T., Peller, M., Knoll, A., Wagenpfeil, S., Minoshima, S., Schwaiger, M., & Kurz, A. (2005) · Neurology · doi:10.1212/01.wnl.0000148478.39691.d3 · Cited by 116 · see citing works
A disorder of cortical GABAergic innervation in Alzheimer's disease
Hardy, J., Cowburn, R. F., BARTON, A. J. L., Reynolds, G. P., Dodd, P. R., Wester, P. O., O’Carroll, A., Lofdahl, E., & Winblad, B. G. (1987) · Neuroscience Letters · doi:10.1016/0304-3940(87)90016-4 · Cited by 114 · see citing works
Brodbeck, J., McGuire, J., Liu, Z., Meyer-Franke, A., Balestra, M. E., Jeong, D.-E., Pleiss, M., McComas, C., Hess, F., Witter, D., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.217380 · Cited by 113 · see citing works
Self-citationMoir, R. D., Atwood, C., Romano, D., Laurans, M. H., Huang, X., Bush, A. I., Smith, J. D., & Tanzi, R. E. (1999) · Biochemistry · doi:10.1021/bi982437d · Cited by 111 · see citing works
Seidl, R., Cairns, N. J., Singewald, N., Kaehler, S. T., & Lübec, G. (2001) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s002100000346 · Cited by 109 · see citing works
Leung, L., Andrews-Zwilling, Y., Yoon, S. Y., Jain, S., Ring, K., Dai, J., Wang, M. M., Tong, L., Walker, D., & Huang, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0053569 · Cited by 109 · see citing works
Self-citationDecreased CSF Concentrations of Homovanillic Acid and γ-Aminobutyric Acid in Alzheimer's Disease
Bareggi, S. R. (1982) · Archives of Neurology · doi:10.1001/archneur.1982.00510230035010 · Cited by 107 · see citing works
Quantitation of apoE Domains in Alzheimer Disease Brain Suggests a Role for apoE in Aß Aggregation
Cho, H. S., Hyman, B. T., Greenberg, S. M., & Rebeck, G. W. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.4.342 · Cited by 100 · see citing works
APOE related alterations in cerebral activation even at college age
Scarmeas, N. (2005) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2004.053645 · Cited by 97 · see citing works
Amyloid β‐Protein, APOE Genotype and Head Injury
Nicoll, J. A. R., Roberts, G. W., & Graham, D. I. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb34431.x · Cited by 96 · see citing works
APOE and the risk of PD with or without dementia in a population-based study
Harhangi, B. S., de Rijk, M. C., van Duijn, C. M., Broeckhoven, C. V., Albert Hofman, D., & Breteler, M. M. B. (2000) · Neurology · doi:10.1212/wnl.54.6.1272 · Cited by 95 · see citing works
Levi, O., & Michaelson, D. M. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04189.x · Cited by 94 · see citing works
Qiu, Z., Hyman, B. T., & Rebeck, G. W. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401055200 · Cited by 93 · see citing works
Grouselle, D., Winsky-Sommerer, R., David, J. P., Delacourte, A., Dournaud, P., & Epelbaum, J. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00698-3 · Cited by 92 · see citing works
Ghosh, S. S., Swerdlow, R. H., Miller, S. W., Sheeman, B., Parker, W. D., & DAVIS, R. E. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07825.x · Cited by 91 · see citing works
Cognitive impairment in PDAPP mice depends on ApoE and ACT-catalyzed amyloid formation
Nilsson, L. N. G., Arendash, G. W., Leighty, R. E., Costa, D. A., Low, M. A., Garcia, M. F., Cracciolo, J. R., Rojiani, A. M., Wu, X., Bales, K. R., et al. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.12.011 · Cited by 87 · see citing works
Brodbeck, J., Balestra, M. E., Saunders, A. M., Roses, A. D., Mahley, R. W., & Huang, Y. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709906104 · Cited by 86 · see citing works
Self-citationJones, P. B., Adams, K. W., Rozkalne, A., Spires-Jones, T. L., Hshieh, T. T., Hashimoto, T., von Armin, C. A. F., Mielke, M., Bacskai, B. J., & Hyman, B. T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014586 · Cited by 84 · see citing works
Genetic variation in the cholesterol 24-hydroxylase (CYP46) gene and the risk of Alzheimer's disease
Desai, P. P., DeKosky, S. T., & Kamboh, M. I. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00443-3 · Cited by 83 · see citing works
Brain metabolic decreases related to the dose of the ApoE e4 allele in Alzheimer's disease
Mosconi, L. (2004) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2003.014993 · Cited by 83 · see citing works
LaClair, K. D., Manaye, K. F., Lee, D. L., Allard, J. S., Savonenko, A. V., Troncoso, J. C., & Wong, P. C. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-18 · Cited by 83 · see citing works
Xu, Q., Brecht, W. J., Weisgraber, K. H., Mahley, R. W., & Huang, Y. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311256200 · Cited by 80 · see citing works
Self-citationTrimmer, P. A., & Borland, M. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.1101 · Cited by 80 · see citing works
Mosconi, L. (2004) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2003.030882 · Cited by 76 · see citing works
Parkinson's Disease and Apolipoprotein E: Possible Association with Dementia but not Age at Onset
Parsian, A., Racette, B. A., Goldsmith, L. J., & Perlmutter, J. S. (2002) · Genomics · doi:10.1006/geno.2002.6707 · Cited by 74 · see citing works
Selective pathological changes of the periaqueductal gray matter in Alzheimer's disease
Parvizi, J., Hoesen, G. W. V., & Damásio, A. R. (2000) · Annals of Neurology · doi:10.1002/1531-8249(200009)48:3 · Cited by 70 · see citing works
Zimmer, R., Teelken, A. W., Trieling, W. B., Weber, W., Weihmayr, T., & Lauter, H. (1984) · Archives of Neurology · doi:10.1001/archneur.1984.04210080010005 · Cited by 67 · see citing works
Feuk, L., Johansson, B. E. A., Bogdanović, N., Johansson, A., Andreasen, N., Lenhard, B., Brookes, A. J., Pedersen, N. L., Blennow, K., Prince, J. A., et al. (2004) · Human Genetics · doi:10.1007/s00439-004-1107-9 · Cited by 62 · see citing works
Association of ABCA1 with late-onset Alzheimer’s disease is not observed in a case-control study
Li, Y., Tacey, K. M., Doil, L. M., van Luchene, R., Garcia, V., Rowland, C. M., Schrodi, S. J., Leong, D. U., Lau, K. F., Catanese, J., et al. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.05.047 · Cited by 62 · see citing works
Age and ApoE genotype interaction in Alzheimer's disease: an FDG-PET study
Mosconi, L., Sorbi, S., Nacmias, B., Cristofaro, M. T. D., Fayyaz, M., Bracco, L., Herholz, K., & Pupi, A. (2004) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2003.12.005 · Cited by 49 · see citing works
Biochemical analysis of cell-derived apoE3 particles active in stimulating neurite outgrowth
Demattos, R. B., Rudel, L. L., & Williams, D. L. (2001) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)31622-9 · Cited by 48 · see citing works
Structural and functional variations in human apolipoprotein E3 and E4.
Chou, C.-Y., Jen, W.-P., Hsieh, Y.-H., Shiao, M.-S., & Chang, G.-G. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m511077200 · Cited by 46 · see citing works
Lesuisse, C. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.22.2525 · Cited by 45 · see citing works
Effect of Carboxyl-Terminal Truncation on Structure and Lipid Interaction of Human Apolipoprotein E4
Tanaka, M., Vedhachalam, C., Sakamoto, T., Dhanasekaran, P., Phillips, M. C., Lund-Katz, S., & Saito, H. (2006) · Biochemistry · doi:10.1021/bi060023b · Cited by 43 · see citing works
The effect of APOE ε4 allele on cerebral glucose metabolism in AD is a function of age at onset
Hirono, N., Hashimoto, M., Yasuda, M., Ishii, K., Sakamoto, S., Kazui, H., & Mori, E. (2002) · Neurology · doi:10.1212/wnl.58.5.743 · Cited by 41 · see citing works
Jain, S., Yoon, S. Y., Leung, L., Knöferle, J., & Huang, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059478 · Cited by 39 · see citing works
Self-citationAPOE ε4 Status and Traumatic Brain Injury on the Gridiron or the Battlefield
Gandy, S., & DeKosky, S. T. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004274 · Cited by 34 · see citing works
Dooren, T. V., Muyllaert, D., Borghgraef, P., Cresens, A., Devijver, H., der Auwera, I. V., Wera, S., Dewachter, I., & LEUVEN, F. V. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.050752 · Cited by 34 · see citing works
Apolipoprotein E4 is probably responsible for the chromosome 19 linkage peak for Parkinson's disease
Martinez, M. M., Brice, A., Vaughan, J. R., et al. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30196 · Cited by 32 · see citing works
Somatostatin genetic variants modify the risk for Alzheimer's disease among Finnish patients
Vepsäläinen, S., Helisalmi, S., Koivisto, A. M., Tapaninen, T., Hiltunen, M. O., & Soininen, H. S. (2007) · Journal of Neurology · doi:10.1007/s00415-007-0539-2 · Cited by 29 · see citing works
Truncated apoE forms tangle-like structures in a neuronal cell line
Ljungberg, M. C., Dayanandan, R., Asuni, A. A., Rupniak, T., Anderton, B. H., & Lovestone, S. (2002) · Neuroreport · doi:10.1097/00001756-200205070-00026 · Cited by 28 · see citing works
The posterior cingulate cortex and anticipatory shifts of spatial attention
Small, D. M., Gitelman, D. R., Gregory, M. D., Nobre, A. C., Parrish, T. B., & Mesulam, M. M. (2001) · NeuroImage · doi:10.1016/s1053-8119(01)91703-3 · Cited by 28 · see citing works
Xue, S., Jia, L., & Jia, J. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.09.002 · Cited by 26 · see citing works
IC‐PL‐02: Do the biomarker findings fit the hypotheses?
Nitsch, R. M. (2009) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2009.05.003 · Cited by 3 · see citing works
Diagnostic criteria for primary progressive mutiple sclerosis: a position paper.
(2000) · Pure Amsterdam UMC · doi:10.1002/1531-8249(200006)47:6 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The amyloid hypothesis of Alzheimer's disease at 25 years
Selkoe, D. J., & Hardy, J. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606210 · Cited by 6,164 · see citing works
Alzheimer's disease: experimental models and reality
Drummond, E., & Wisniewski, T. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1662-x · Cited by 810 · see citing works
Impact of multiple pathologies on the threshold for clinically overt dementia
Kapasi, A., DeCarli, C., & Schneider, J. A. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1717-7 · Cited by 739 · see citing works
Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease
Nelson, A. R., Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.12.016 · Cited by 559 · see citing works
A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward
Belloy, M. E., Napolioni, V., & Greicius, M. D. (2019) · Neuron · doi:10.1016/j.neuron.2019.01.056 · Cited by 570 · see citing works
Liu, L., MacKenzie, K. R., Putluri, N., Maletić-Savatić, M., & Bellen, H. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.024 · Cited by 556 · see citing works
Circadian Rhythms, Sleep, and Disorders of Aging
Mattis, J., & Sehgal, A. (2016) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2016.02.003 · Cited by 369 · see citing works
Nanoparticle protein corona: from structure and function to therapeutic targeting
Bashiri, G., Padilla, M. S., Swingle, K. L., Shepherd, S. J., Mitchell, M. J., & Wang, K. (2023) · Lab on a Chip · doi:10.1039/d2lc00799a · Cited by 296 · see citing works
Amyloid-β Receptors: The Good, the Bad, and the Prion Protein
Jarosz-Griffiths, H. H., Noble, E., Rushworth, J. V., & Hooper, N. M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.702704 · Cited by 256 · see citing works
Down Syndrome, Partial Trisomy 21, and Absence of Alzheimer’s Disease: The Role of APP
Doran, E., Keator, D., Head, E., Phelan, M. J., Kim, R., Totoiu, M., Barrio, J. R., Small, G. W., Potkin, S. G., & Lott, I. T. (2017) · Journal of Alzheimer’s Disease · doi:10.3233/jad-160836 · Cited by 244 · see citing works
Apolipoprotein E and Alzheimer’s disease: Findings, hypotheses, and potential mechanisms
Koutsodendris, N., Nelson, M. R., Rao, A., & Huang, Y. (2022) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-030421-112756 · Cited by 231 · see citing works
Self-citationSolomon, A., Turunen, H., Ngandu, T., Peltonen, M., Levälahti, E., Helisalmi, S., Antikainen, R., Bäckman, L., Hänninen, T., Jula, A., et al. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2017.4365 · Cited by 213 · see citing works
Blood–Brain Barrier Breakdown in Alzheimer’s Disease: Mechanisms and Targeted Strategies
Alkhalifa, A. E., Al-Ghraiybah, N. F., Odum, J., Shunnarah, J. G., Austin, N., & Kaddoumi, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216288 · Cited by 212 · see citing works
Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease
Najm, R., Jones, E. A., & Huang, Y. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0324-6 · Cited by 183 · see citing works
Self-citationApolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease
Liao, F., Yoon, H., & Kim, J. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000383 · Cited by 191 · see citing works
“In the plasma, ApoE4 associates Volume 28 Number 1 February 2017 preferentially with large, triglyceride-rich VLDL particles while ApoE2 and ApoE3 have a preference for small, phospholipid-rich HDL [3].”
BackgroundInfluentialTargeting 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 gene variants in primary dyslipidemia
Khalil, Y. A., Rabès, J.-P., Boileau, C., & Varret, M. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.05.007 · Cited by 170 · see citing works
Martins, R. N., Villemagne, V., Sohrabi, H. R., Chatterjee, P., Shah, T. M., Verdile, G., Fraser, P., Taddei, K., Gupta, V. B., Rainey-Smith, S. R., et al. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-171145 · Cited by 129 · see citing works
Nelson, M. R., Liu, P., Agrawal, A., Yip, O., Blumenfeld, J., Traglia, M., Kim, M. J., Koutsodendris, N., Rao, A., Grone, B., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01480-8 · Cited by 118 · see citing works
Self-citationAPOE alters glucose flux through central carbon pathways in astrocytes
Williams, H. C., Farmer, B. C., Piron, M. A., Walsh, A. E., Bruntz, R. C., Gentry, M. S., Sun, R. C., & Johnson, L. A. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104742 · Cited by 105 · see citing works
Association of Rare <i>APOE</i> 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
Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease
Butterfield, D. A., & Boyd-Kimball, D. (2020) · Antioxidants · doi:10.3390/antiox9090818 · Cited by 85 · see citing works
Roses, A., Sundseth, S., Saunders, A., Gottschalk, W., Burns, D., & Lutz, M. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.015 · Cited by 70 · see citing works
Midlife lipid and glucose levels are associated with Alzheimer's disease
Zhang, X., Tong, T., Chang, A., Ang, T. F. A., Tao, Q., Auerbach, S., Devine, S., Qiu, W. Q., Mez, J., Massaro, J., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.12641 · Cited by 65 · see citing works
Apolipoproteins: New players in cancers
He, Y., Chen, J., Ma, Y., & Chen, H. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1051280 · Cited by 52 · see citing works
APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline
Fang, W., Xiao, N., Zeng, G., Bi, D., Dai, X., Mi, X., Ye, Q., Chen, X., & Zhang, J. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01631-0 · Cited by 42 · see citing works
Mullane, K., & Williams, M. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.09.027 · Cited by 32 · see citing works
Opposing Roles of apolipoprotein E in aging and neurodegeneration
Hudry, E., Klickstein, J., Cannavo, C., Jackson, R., Muzikansky, A., Gandhi, S., Urick, D., Sargent, T., Wrobleski, L., Roe, A. D., et al. (2019) · Life Science Alliance · doi:10.26508/lsa.201900325 · Cited by 30 · see citing works
Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis
More, S., Bonnereau, J., Wouters, D., Spotbeen, X., Karras, P., Rizzollo, F., Killian, T., Venken, T., Naulaerts, S., Vervoort, E., et al. (2024) · Science Advances · doi:10.1126/sciadv.adp6164 · Cited by 25 · see citing works
Zhao, J., Ikezu, T. C., Lu, W., Macyczko, J. R., Li, Y., Lewis-Tuffin, L. J., Martens, Y. A., Ren, Y., Zhu, Y., Asmann, Y. W., et al. (2023) · Stem Cell Research & Therapy · doi:10.1186/s13287-023-03444-y · Cited by 25 · see citing works
High-density lipoprotein-related cholesterol metabolism in Alzheimer's disease
Pedrini, S., Chatterjee, P., Hone, E., & Martins, R. N. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15170 · Cited by 22 · see citing works
Katsarou, M., Stratikos, E., & Chroni, A. (2018) · Journal of Lipid Research · doi:10.1194/jlr.m088732 · Cited by 22 · see citing works
Gal, J., Katsumata, Y., Zhu, H., Srinivasan, S., Chen, J., Johnson, L. A., Wang, W.-X., Golden, L. R., Wilcock, D. M., Jicha, G. A., et al. (2022) · The American Journal of Pathology · doi:10.1016/j.ajpath.2021.11.013 · Cited by 17 · see citing works
Apolipoprotein E2 Stimulates Protein Synthesis and Promotes Melanoma Progression and Metastasis
Adaku, N., Ostendorf, B. N., Mei, W., & Tavazoie, S. F. (2023) · Cancer Research · doi:10.1158/0008-5472.can-23-1252 · Cited by 15 · see citing works
Childhood socioeconomic position and later-life cognitive functioning in the U.S.: A critical review
Skoblow, H. F., Proulx, C. M., & Palermo, F. (2024) · Developmental Review · doi:10.1016/j.dr.2023.101104 · Cited by 10 · see citing works
Pineda‐Lopez, L., Aguillon, D., Villar‐Vesga, J., Valderrama‐Carmona, P., Guerrero, A., Upreti, A., Arevalo‐Alquichire, S., Correa, L., Mendez‐Castellanos, K., Castaño, D., et al. (2026) · Alzheimer's & Dementia · doi:10.1002/alz.71148 · Cited by 4 · see citing works
Imaging and rare <i>APOE</i> alleles: Alzheimer disease as a developmental disorder
Knickmeyer, R. C., & Ross, M. E. (2016) · Neurology · doi:10.1212/wnl.0000000000002956 · Cited by 3 · see citing works
Burton, E. A., Argenziano, M., Cook, K., Ridler, M., Lu, S., Su, C., Manduchi, E., Littleton, S. H., Leonard, M. E., Hodge, K. M., et al. (2024) · doi:10.1101/2024.08.22.609230 · Cited by 3 · see citing works
ApoE expression across the CNS: Who, What, Where, When, and How (much)?
Nolt, G. L., Lucido, C. C., Smith, L. M., & Johnson, L. A. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00028-x · Cited by 2 · see citing works
Hernandez Arriaza, R., Reil, D., Fatuzzo, N., Fu, M., Dai, Y., Fernandez Martinez, D., Jiang, H., Holtzman, D. M., Greicius, M. D., & Khosla, C. (2025) · Biochemistry · doi:10.1021/acs.biochem.5c00503 · Cited by 2 · see citing works
Tang, J.-Y., Tan, Q., Yu, Z.-Y., Yuan, Z.-Y., Zeng, R., Liu, X.-Y., Zhu, X.-Y., Zhao, Y., Li, J.-H., Bai, Y.-D., et al. (2026) · Neuron · doi:10.1016/j.neuron.2026.04.027
Rodriguez Martinez, P. J., Yslas, A. R., Inoue, Y., Parsons, T. M., Baker, S. K., Lu, W., Raulin, A.-C., & Kanekiyo, T. (2026) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2026.1778856
The First Case of Lipoprotein Glomerulopathy in a Patient With Male Infertility
Ye, C., Wang, Y., Liang, C., Wang, Y., Zhang, C., & Jiang, H. (2026) · Kidney Medicine · doi:10.1016/j.xkme.2026.101308
Hsu, C.-H., Chu, P.-W., Chen, Y.-Y., Ho, M.-H., Liao, E.-C., & Chen, S.-K. (2026) · Neurochemical Research · doi:10.1007/s11064-026-04842-3
- Authors
- Huang, Y., & Mahley, R. W.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Huang, Yadong
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 72
- Pages
- 3-12
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC4253862
- OpenAlex
- W2056516296
- Cited by
- 829
- References
- 153
- Citations by year
- 2026: 89 · 2025: 130 · 2024: 113 · 2023: 86 · 2022: 90 · 2021: 79 · 2020: 59 · 2019: 54 · 2018: 41 · 2017: 34 · 2016: 37 · 2015: 16
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Heath (P50AG023501, 1RF1AG047655, 2P50AG023501)
- S.D. Bechtel, Jr. Foundation
- Hellman Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein E, APOE isoforms, APOE ε4, lipid metabolism, neurobiology, Alzheimer's disease, lipoprotein binding, cell surface receptors, lipid redistribution, cytoskeletal assembly, mitochondrial function, dendritic morphology, protein structure, neurodegeneration
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Brain, Disease Models, Animal, Humans, Protein Binding, Lipid Metabolism, Mice
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
