Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer’s disease

Mahley, Robert W.; Weisgraber, Karl H.; Huang, Yadong

doi:10.1073/pnas.0600549103

Cited by 912Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsLipoproteins and Cardiovascular Health

Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer’s disease

Open access

Mahley, Robert W., Weisgraber, Karl H., Huang, Yadong·2006·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0600549103PMC PMC1414631

Open this paper in CoChat — free account

Abstract

The premise of this review is that apolipoprotein (apo) E4 is much more than a contributing factor to neurodegeneration. ApoE has critical functions in redistributing lipids among CNS cells for normal lipid homeostasis, repairing injured neurons, maintaining synapto-dendritic connections, and scavenging toxins. In multiple pathways affecting neuropathology, including Alzheimer’s disease, apoE acts directly or in concert with age, head injury, oxidative stress, ischemia, inflammation, and excess amyloid β peptide production to cause neurological disorders, accelerating progression, altering prognosis, or lowering age of onset. We envision that unique structural features of apoE4 are responsible for apoE4-associated neuropathology. Although the structures of apoE2, apoE3, and apoE4 are in dynamic equilibrium, apoE4, which is detrimental in a variety of neurological disorders, is more likely to assume a pathological conformation. Importantly, apoE4 displays domain interaction (an interaction between the N- and C-terminal domains of the protein that results in a compact structure) and molten globule formation (the formation of stable, reactive intermediates with potentially pathological activities). In response to CNS stress or injury, neurons can synthesize apoE. ApoE4 uniquely undergoes neuron-specific proteolysis, resulting in bioactive toxic fragments that enter the cytosol, alter the cytoskeleton, disrupt mitochondrial energy balance, and cause cell death. Our findings suggest potential therapeutic strategies, including the use of “structure correctors” to convert apoE4 to an “apoE3-like” molecule, protease inhibitors to prevent the generation of toxic apoE4 fragments, and “mitochondrial protectors” to prevent cellular energy disruption.

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

Crossref · 10.1073/pnas.0600549103

Cites

166 of 166 references verified0 citation errors · 0 not checkable

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 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 [2]
The “ApoE and Neuropathology” section calls apoE4 the major known genetic risk factor for Alzheimer’s disease in many populations. It does not specify late-onset disease, and the citing sentence omits the population qualifier. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Most AD patients have sporadic late-onset AD, in which the APOE gene contains a predominant risk variant.
“Most AD patients have sporadic late-onset AD (LOAD), in which the apolipoprotein E (APOE) gene contains a predominant risk variant6,7.”
From APOE3 - R136S mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition (2024) · cites this paper as [6]
The ‘ApoE and Neuropathology’ section identifies apoE4 as the major known genetic risk factor for AD in many populations. It does not establish that most AD patients have sporadic late-onset AD or specifically tie that risk-factor statement to late-onset disease. (LLM, conf=0.85)
Experimental — accuracy not yet measured
In neurons, apoE4 is associated with impaired mitochondrial respiration.
“In neurons, apoE4 is associated with impaired mitochondrial respiration”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [10]
The section “ApoE4 Neuropathology Independent of Aβ” (page unavailable) associates apoE4 with reduced neuronal glucose utilization and describes mitochondrial dysfunction in cultured neurons. That supports impaired mitochondrial function, but the paper does not specifically establish impaired mitochondrial respiration. (LLM, conf=0.82)
Experimental — accuracy not yet measured
The largest apoE4 fragment, apoE4(1-272), causes mitochondrial fragmentation.
“and cause mitochondrial fragmentation [10, 17, 20]”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [10]
In “ApoE4 Neuropathology Independent of Aβ” (page unavailable), the paper says apoE4(1-272) accumulates in mitochondria and describes mitochondrial dysfunction associated with apoE fragments. It does not say that apoE4(1-272) causes mitochondrial fragmentation, a distinct change in mitochondrial structure. (LLM, conf=0.84)
Experimental — accuracy not yet measured
The largest apoE4 fragment, apoE4(1-272), interacts directly with mitochondria to reduce mitochondrial membrane potential.
“The largest apoE4 fragment, apoE4(1–272), interacts directly with mitochondria to reduce mitochondrial membrane potential”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [10]
In “ApoE4 Neuropathology Independent of Aβ” (page unavailable), the paper reports that apoE4(1–272) accumulates in mitochondria and that apoE fragments disrupt mitochondrial electropotential in cultured neurons. It does not establish that apoE4(1–272) directly binds mitochondria: the Mitochondrial Binding subsection says how the fragments associate with mitochondria is unknown and offers direct binding as one possibility. (LLM, conf=0.87)
Experimental — accuracy not yet measured

ApoE4 lipid-binding region (240-270 aa) in the C-terminal domain is involved in direct interaction with mitochondria and binding to Aβ.
“while the lipid-binding region (240–270 aa) in the C-terminal domain is more likely involved in direct interaction with mitochondria (Figure 1) and binding to Aβ [26].”
From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [26]
The Fig. 4 caption identifies residues 240–270 as a lipid- and Aβ-binding region involved in mitochondrial localization. But the “Mitochondrial Binding” section says the authors do not know how apoE fragments associate with mitochondria: direct lipid binding is one possibility alongside indirect routes. The source therefore does not establish that direct interaction is more likely. Page numbers were not provided in the excerpts. (LLM, conf=0.87)
Experimental — accuracy not yet measured
ApoE4 receptor-binding region (136-150 aa) is required for binding to the LDL receptor and to tau protein.
“Within the N-terminal domain, ApoE4 receptor-binding region (136–150 aa) is required for its binding to the low-density lipoprotein (LDL) receptor and to tau protein”
From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [26]
The Fig. 4 caption (ApoE4 Neuropathology in the Context of Aβ) says residues 136–150 play a key role in binding to the LDL receptor and tau, and Structural Differences Among the ApoE Isoforms identifies them as the LDL receptor-binding site. But ApoE4 Effects on Tau Phosphorylation says apoE4 does not interact significantly with tau in vitro, unlike apoE3. The source therefore does not establish that this region is required for apoE4 to bind tau. (LLM, conf=0.86)
Experimental — accuracy not yet measured
ApoE4 largest fragment (1-272 aa) directly interacts with mitochondria, leading to decrease in Δψm and mitochondrial fragmentation.
“ApoE4 largest fragment (1–272 aa) was shown to directly interact with mitochondria, which leads to a decrease in Δψm and mitochondrial fragmentation [26,29,73].”
From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [26]
The “ApoE4 Neuropathology Independent of Aβ” section reports that apoE4(1–272) accumulates in mitochondria and that apoE fragments disrupt mitochondrial electropotential in cultured neurons. It does not report mitochondrial fragmentation, and it explicitly says how the fragments associate with mitochondria is unknown, so direct interaction is not established. (LLM, conf=0.88)
Experimental — accuracy not yet measured
The observed difference in Aβ deposition between apoE isoforms cannot be simply attributed to apoE4 levels being lower than apoE3.
“However, the structure of apoE3 and apoE4 differs significantly from each other (Mahley et al., 2006), and the observed difference in Aβ deposition cannot be simply attributed to apoE4 levels being lower than apoE3.”
From Haploinsufficiency of Human APOE Reduces Amyloid Deposition in a Mouse Model of Amyloid-β Amyloidosis (2011) · cites this paper as Mahley et al., 2006
Recently identified functional siRNA sequences target Apolipoprotein E (ApoE), implicated in several neurodegenerative diseases.
“Recently, we identified functional siRNA sequences targeting Apolipoprotein E (ApoE), implicated in several neurodegenerative diseases, including Alzheimer’s disease and Amyotrophic Lateral Sclerosis26–28 (Ferguson et al., manuscript in preparation).”
From A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system (2019) · cites this paper as [27]
Apolipoprotein E is believed to play a critical role in brain function.
“Because apoE is believed to play a critical role in brain function11”
From Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function (2014) · cites this paper as [11]
ApoE4 has been associated with a variety of neuropathological processes, including Alzheimer disease (AD).
“ApoE4 has been associated with a variety of neuropathological processes, including Alzheimer disease (AD) (2).”
From Molecular Basis for Increased Risk for Late-onset Alzheimer Disease Due to the Naturally Occurring L28P Mutation in Apolipoprotein E4 (2014) · cites this paper as [2]
ApoE4 lowers the age of onset of Alzheimer's disease.
“lowers the age of onset [4–14]”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [10]
In neurons, apoE4 is associated with neurotoxicity.
“and neurotoxicity [10, 17–19, 34, 35]”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [10]
In neurons, apoE4 is associated with decreased neurite outgrowth.
“decreased neurite outgrowth”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [10]
ApoE4 increases risk for Alzheimer's disease.
“ApoE4 increases risk for AD”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [10]
Several proteases are suggested to be responsible for ApoE4 cleavage at different sites, including collagenase, MMP-9, neuron-specific α-chymotrypsin-like serine protease, cathepsin D, and HtrA1.
“Several proteases have been suggested to be responsible for ApoE4 cleavage at different sites, including collagenase, matrix metalloproteinas-9 (MMP-9) [25], neuron-specific α-chymotrypsin-like serine protease [26], cathepsin D (the only aspartic protease identified) [27] and high-temperature requirement serine protease A1 (HtrA1) [21].”
From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [26]
The three common apoE isoforms differ by only one or two amino acids at residue 112 or 158, but these differences profoundly alter apoE structure and function.
“Although the three common isoforms differ by only one or two amino-acids at residue 112 or 158, these differences profoundly alter apoE structure and function (Mahley et al., 2006).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Mahley et al., 2006
The 29 kDa amino-terminal fragment generated by chymotrypsin-like serine protease has been shown to induce cytoskeletal disruptions and perturb mitochondrial energy balance.
“The 29 kDa amino-terminal fragment generated by chymotrypsin-like serine protease has been shown to induce cytoskeletal disruptions and perturb mitochondrial energy balance.”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Mahley et al., 2006
Along with Aβ-independent intrinsic toxicities, apoE4 has been shown to exacerbate neurotoxicity triggered by Aβ and other insults.
“Along with Aβ-independent intrinsic toxicities, apoE4 has been shown to exacerbate neurotoxicity triggered by A and other insults (Mahley et al., 2006).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Mahley et al., 2006
One of the most extensively investigated direct toxic mechanisms involves the 29 kDa carboxyl-terminal-truncated fragment of apoE4 (amino acid 1-272 residues).
“One of the most extensively investigated direct toxic mechanisms involves the 29 kDa carboxyl-terminal-truncated fragment of apoE4 (amino acid 1–272 residues) (Mahley et al., 2007; Mahley et al., 2006).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Mahley et al., 2006
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 [14]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · see citing works
Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
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-citation
Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786 · see citing works
In Vivo Protein Transduction: Delivery of a Biologically Active Protein into the Mouse
Schwarze, S. R., Ho, A. L., Vocero-Akbani, A. M., & Dowdy, S. F. (1999) · Science · doi:10.1126/science.285.5433.1569 · Cited by 2,418 · see citing works
A Truncated HIV-1 Tat Protein Basic Domain Rapidly Translocates through the Plasma Membrane and Accumulates in the Cell Nucleus
Vivès, É., Brodin, P. M., & Lebleu, B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.25.16010 · Cited by 2,377 · see citing works
Close Contacts with the Endoplasmic Reticulum as Determinants of Mitochondrial Ca 2+ Responses
Rizzuto, R., Pinton, P., Carrington, W., Fay, F. S., Fogarty, K. E., Lifshitz, L. M., Tuft, R. A., & Pozzan, T. (1998) · Science · doi:10.1126/science.280.5370.1763 · Cited by 2,257 · see citing works
Alzheimer’s Dementia
Melnick, V. L., & Dubler, N. N. (1985) · Contemporary Issues in Biomedicine, Ethics, and Society · doi:10.1007/978-1-4612-5174-3 · Cited by 1,986 · see citing works
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920 · see citing works
Apolipoprotein E: Far More Than a Lipid Transport Protein
Mahley, R. W., & Rall, S. C. (2000) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.1.1.507 · Cited by 1,836 · see citing works
Self-citation
The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses
Li, Z., Okamoto, K.-I., Hayashi, Y., & Sheng, M. (2004) · Cell · doi:10.1016/j.cell.2004.11.003 · Cited by 1,498 · see citing works
Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease.
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
Self-citation
Toxic Proteins in Neurodegenerative Disease
Taylor, J. P., Hardy, J., & Fischbeck, K. H. (2002) · Science · doi:10.1126/science.1067122 · Cited by 1,251 · see citing works
Tat-mediated delivery of heterologous proteins into cells.
Fawell, S. E., Seery, J., Daikh, Y., Moore, C., Chen, L. L., Pepinsky, B., & Barsoum, J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.2.664 · Cited by 1,225 · see citing works
Molten Globule and Protein Folding
Ptitsyn, O. B. (1995) · Advances in protein chemistry · doi:10.1016/s0065-3233(08)60546-x · Cited by 1,222 · see citing works
DOCK 4.0: Search strategies for automated molecular docking of flexible molecule databases
Ewing, T. J. A., Makino, S., Skillman, A. G., & Kuntz, I. D. (2001) · Journal of Computer-Aided Molecular Design · doi:10.1023/a:1011115820450 · Cited by 1,188 · see citing works
Phospholipid synthesis in a membrane fraction associated with mitochondria.
Vance, J. E. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39106-9 · Cited by 1,153 · see citing works
Structure-Based Strategies for Drug Design and Discovery
Kuntz, I. D. (1992) · Science · doi:10.1126/science.257.5073.1078 · Cited by 989 · 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
Automated docking with grid‐based energy evaluation
Meng, E. C., Shoichet, B. K., & Kuntz, I. D. (1992) · Journal of Computational Chemistry · doi:10.1002/jcc.540130412 · Cited by 949 · see citing works
Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease
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
The structural basis of protein folding and its links with human disease
Dobson, C. M. (2001) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2000.0758 · Cited by 934 · see citing works
Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70
Young, J. C., Hoogenraad, N. J., & Hartl, F. U. (2003) · Cell · doi:10.1016/s0092-8674(02)01250-3 · Cited by 915 · see citing works
Apolipoprotein E allele–specific antioxidant activity and effects on cytotoxicity by oxidative insults and β–amyloid peptides
Miyata, M., & Smith, J. D. (1996) · Nature Genetics · doi:10.1038/ng0996-55 · Cited by 891 · see citing works
Amyloid-associated proteins α1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments
Ma, J., Yee, A., Brewer, H. B., Das, S., & Potter, H. (1994) · Nature · doi:10.1038/372092a0 · Cited by 871 · 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
Self-citation
Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system.
Boyles, J. K., Pitas, R. E., Wilson, E., Mahley, R. W., & Taylor, J. M. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112130 · Cited by 829 · see citing works
Self-citation
Cell-penetrating peptides
Lindgren, M., Hällbrink, M., Prochiantz, A., & Langel, Ü. (2000) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01447-4 · Cited by 806 · 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-citation
Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer’s disease
Small, G. W., Ercoli, L. M., Silverman, D. H. S., Huang, S.-C., Komo, S., Bookheimer, S. Y., Lavretsky, H., Miller, K., Siddarth, P., Rasgon, N. L., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.090106797 · Cited by 790 · see citing works
The <EMPH TYPE="ITAL">APOE</EMPH>-∊4 Allele and the Risk of Alzheimer Disease Among African Americans, Whites, and Hispanics
Tang, M.-X. (1998) · JAMA · doi:10.1001/jama.279.10.751 · Cited by 771 · see citing works
Trojan peptides: the penetratin system for intracellular delivery
Derossi, D., Chassaing, G., & Prochiantz, A. (1998) · Trends in Cell Biology · doi:10.1016/s0962-8924(98)80017-2 · Cited by 725 · see citing works
Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain.
Pitas, R. E., Boyles, J. K., Lee, S. H., Hui, D., & Weisgraber, K. H. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47945-8 · Cited by 714 · see citing works
Self-citation
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
Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins
Pitas, R. E., Boyles, J. K., Lee, S. H., Foss, D., & Mahley, R. W. (1987) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(87)90295-5 · Cited by 693 · see citing works
Self-citation
Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease
Risner, M. E., Saunders, A. M., Altman, J. F. B., Ormandy, G. C., Craft, S., Foley, I. M., Zvartau-Hind, M. E., Hosford, D. A., Roses, A. D., & for the Rosiglitazone in Alzheimer's Disease Study Group (2006) · The Pharmacogenomics Journal · doi:10.1038/sj.tpj.6500369 · Cited by 686 · see citing works
Association 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
Three-Dimensional Structure of the LDL Receptor-Binding Domain of Human Apolipoprotein E
Wilson, C., Wardell, M. R., Weisgraber, K. H., Mahley, R. W., & Agard, D. A. (1991) · Science · doi:10.1126/science.2063194 · Cited by 678 · see citing works
Self-citation
Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing
Jordan, B. D. (1997) · JAMA · doi:10.1001/jama.278.2.136 · Cited by 659 · see citing works
Accelerated transport and maturation of lysosomal α–galactosidase A in Fabry lymphoblasts by an enzyme inhibitor
Fan, J., Ishii, S., Asano, N., & Suzuki, Y. (1999) · Nature Medicine · doi:10.1038/4801 · Cited by 616 · see citing works
Apolipoprotein E Type 4 Allele and Cerebral Glucose Metabolism in Relatives at Risk for Familial Alzheimer Disease
Small, G. W. (1995) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1995.03520360056039 · Cited by 604 · see citing works
Expression of apolipoprotein E during nerve degeneration and regeneration.
Ignatius, M. J., Gebicke‐Haerter, P. J., Skene, J. H. P., Schilling, J., Weisgraber, K. H., Mahley, R. W., & Shooter, E. M. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.4.1125 · Cited by 568 · see citing works
Self-citation
Small-molecule correctors of defective F508-CFTR cellular processing identified by high-throughput screening
Pedemonte, N. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24898 · Cited by 542 · 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
A role for apolipoprotein E, apolipoprotein A-I, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve.
Boyles, J. K., Zoellner, C. D., Anderson, L. J., Kosik, L. M., Pitas, R. E., Weisgraber, K. H., Hui, D. Y., Mahley, R. W., Gebicke‐Haerter, P. J., & Ignatius, M. J. (1989) · Journal of Clinical Investigation · doi:10.1172/jci113943 · Cited by 533 · see citing works
Self-citation
Apolipoprotein E mRNA is abundant in the brain and adrenals, as well as in the liver, and is present in other peripheral tissues of rats and marmosets.
Elshourbagy, N. A., Liao, W. S. ‐., Mahley, R. W., & Taylor, J. M. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.1.203 · Cited by 509 · see citing works
Self-citation
Apolipoprotein E is essential for amyloid deposition in the APP V717F transgenic mouse model of Alzheimer's disease
Bales, 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
Endocytosis and targeting of exogenous HIV‐1 Tat protein.
Mann, D. A., & Frankel, A. D. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb07697.x · Cited by 485 · see citing works
Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease.
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
Self-citation
Declining brain activity in cognitively normal apolipoprotein E ɛ4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease
Reiman, E. M., Caselli, R. J., Chen, K., Alexander, G. E., Bandy, D., & Frost, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.061509598 · Cited by 467 · see citing works
Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia): questions, quandaries, and paradoxes
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-citation
Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro.
(1994) · PubMed Central · Cited by 441 · 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
Hypothesis: Microtubule Instability and Paired Helical Filament Formation in the Alzheimer Disease Brain Are Related to Apolipoprotein E Genotype
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
Self-citation
In VivoDelivery of a Bcl-xL Fusion Protein Containing the TAT Protein Transduction Domain Protects against Ischemic Brain Injury and Neuronal Apoptosis
Cao, G., Pei, W., Ge, H., Liang, Q., Luo, Y., Sharp, F. R., Lu, A., Ran, R., Graham, S. H., & Chen, J. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-13-05423.2002 · Cited by 420 · see citing works
Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3
Sanan, D. A., Weisgraber, K. H., Russell, S. J., Mahley, R. W., Huang, D., Saunders, A., Schmechel, D., Wisniewski, T., Frangione, B., & Roses, A. D. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117407 · Cited by 404 · see citing works
Self-citation
Neuron-Specific Apolipoprotein E4 Proteolysis Is Associated with Increased Tau Phosphorylation in Brains of Transgenic Mice
Brecht, 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-citation
Molecular docking to ensembles of protein structures 1 1Edited by B. Honig
Knegtel, R. M. A., Kuntz, I. D., & Oshiro, C. M. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0776 · Cited by 393 · see citing works
Apolipoprotein E fragments present in Alzheimer's disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons
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-citation
Apolipoprotein E
Mahley, R. W., & Huang, Y. (1999) · Current Opinion in Lipidology · doi:10.1097/00041433-199906000-00003 · Cited by 388 · see citing works
Self-citation
Isoform-specific effects of human apolipoprotein E on brain function revealed in ApoE knockout mice: Increased susceptibility of females
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-citation
Expression of Human Apolipoprotein E3 or E4 in the Brains ofApoe−/−Mice: Isoform-Specific Effects on Neurodegeneration
Buttini, 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-citation
Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line.
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-citation
Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice
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-citation
Human apolipoprotein E: the Alzheimer's disease connection
Weisgraber, K. H., & Mahley, R. W. (1996) · The FASEB Journal · doi:10.1096/fasebj.10.13.8940294 · Cited by 327 · see citing works
Self-citation
Human apolipoprotein E: Role of arginine 61 in mediating the lipoprotein preferences of the E3 and E4 isoforms
Dong, L. M., Wilson, C., Wardell, M. R., Simmons, T., Mahley, R. W., Weisgraber, K. H., & Agard, D. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31797-0 · Cited by 320 · see citing works
Self-citation
Lipid- and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity
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-citation
Human Apolipoprotein E4 Domain Interaction
Dong, L.-M., & Weisgraber, K. H. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.32.19053 · Cited by 318 · see citing works
Self-citation
Apolipoprotein 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
Differences in stability among the human apolipoprotein E isoforms determined by the amino-terminal domain
Morrow, J. A., Segall, M. L., Lund-Katz, S., Phillips, M. C., Knapp, M., Rupp, B., & Weisgraber, K. H. (2000) · Biochemistry · doi:10.1021/bi000099m · Cited by 315 · see citing works
Self-citation
Stable expression and secretion of apolipoproteins E3 and E4 in mouse neuroblastoma cells produces differential effects on neurite outgrowth
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-citation
Apolipoprotein E distribution among human plasma lipoproteins: role of the cysteine-arginine interchange at residue 112
Weisgraber, K. H. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42621-5 · Cited by 304 · see citing works
Self-citation
New optimization method for conformational energy calculations on polypeptides: Conformational space annealing
Lee, J., Scheraga, H. A., & Rackovsky, S. R. (1997) · Journal of Computational Chemistry · doi:10.1002/(sici)1096-987x(19970715)18:9 · Cited by 300 · see citing works
Cognitive change and the APOE ɛ4 allele
Deary, I. J., Whiteman, M. C., Pattie, A., Starr, J. M., Hayward, C., Wright, A. F., Carothers, A. D., & Whalley, L. J. (2002) · Nature · doi:10.1038/418932a · Cited by 296 · see citing works
Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes
Diedrich, J. F., Minnigan, H. J., Carp, R. I., Whitaker, J. N., Race, R., Frey, W. H., & Haase, A. T. (1991) · Journal of Virology · doi:10.1128/jvi.65.9.4759-4768.1991 · Cited by 295 · see citing works
ApoE 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
The inhibitory effect of apolipoprotein E4 on neurite outgrowth is associated with microtubule depolymerization
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-citation
Apolipoprotein (apo) E4 enhances amyloid β peptide production in cultured neuronal cells: ApoE structure as a potential therapeutic target
Ye, S., Huang, Y., Müllendorff, K., Dong, L., Giedt, G., Meng, E. C., Cohen, F. E., Kuntz, I. D., Weisgraber, K. H., & Mahley, R. W. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508693102 · Cited by 275 · see citing works
Self-citation
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
Preliminary Report of a Genetic Basis for Cognitive Decline After Cardiac Operations
Tardiff, B. E., Newman, M. F., Saunders, A. M., Strittmatter, W. J., Blumenthal, J. A., White, W. D., Croughwell, N. D., Davis, R. D., Roses, A. D., & Reves, J. G. (1997) · The Annals of Thoracic Surgery · doi:10.1016/s0003-4975(97)00757-1 · Cited by 256 · see citing works
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
Self-citation
Expression of Human Apolipoprotein E4 in Neurons Causes Hyperphosphorylation of Protein Tau in the Brains of Transgenic Mice
Tesseur, 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-citation
Unique Lipoproteins Secreted by Primary Astrocytes From Wild Type, apoE (−/−), and Human apoE Transgenic Mice
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
Apolipoprotein E (ApoE) isoform-dependent lipid release from astrocytes prepared from human ApoE3 and ApoE4 knock-in mice
Gong, J.-S., Kobayashi, M., Hayashi, H., Zou, K., Sawamura, N., Fujita, S. C., Yanagisawa, K., & Michikawa, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203934200 · Cited by 214 · see citing works
Glial fibrillary acidic protein-apolipoprotein E (apoE) transgenic mice: astrocyte-specific expression and differing biological effects of astrocyte-secreted apoE3 and apoE4 lipoproteins.
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
Predictors of cognitive decline after cardiac operation
Newman, M. F., Croughwell, N. D., Blumenthal, J. A., Lowry, E., White, W. D., Spillane, W., Davis, R. D., Glower, D. D., Smith, L. R., Mahanna, E. P., et al. (1995) · The Annals of Thoracic Surgery · doi:10.1016/0003-4975(95)00076-w · Cited by 210 · see citing works
APOE ε4 is associated with obstructive sleep apnea/hypopnea
Gottlieb, D. J., DeStefano, A. L., Foley, D., Mignot, E. J.-M., Redline, S. S., Givelber, R. J., & Young, T. B. (2004) · Neurology · doi:10.1212/01.wnl.0000134671.99649.32 · Cited by 207 · see citing works
Lipoprotein Uptake by Neuronal Growth Cones in Vitro
Ignatius, M. J., Shooter, E. M., Pitas, R. E., & Mahley, R. W. (1987) · Science · doi:10.1126/science.3576212 · Cited by 207 · see citing works
Self-citation
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
Apolipoprotein E4 Forms a Molten Globule
Morrow, J. A., Hatters, D. M., Lu, B., Höchtl, P., Oberg, K. A., Rupp, B., & Weisgraber, K. H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204898200 · Cited by 204 · see citing works
Self-citation
Apolipoprotein E is localized to the cytoplasm of human cortical neurons: a light and electron microscopic study
Han, S.-H., Einstein, G., Weisgraber, K. H., Strittmatter, W. J., Saunders, A. M., Pericak-Vance, M., Roses, A. D., & Schmechel, D. E. (1994) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199409000-00013 · Cited by 195 · see citing works
Self-citation
Introduction of human apolipoprotein E4 “domain interaction” into mouse apolipoprotein E
Raffaı̈, R. L., Dong, L., Farese, R. V., & Weisgraber, K. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.201279298 · Cited by 192 · see citing works
Self-citation
Lysosomal Membrane Damage in Soluble Aβ-Mediated Cell Death in Alzheimer's Disease
Ditaranto, K., Tekirian, T. L., & Yang, A. J. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0364 · Cited by 192 · see citing works
Androgens Protect against Apolipoprotein E4-Induced Cognitive Deficits
Raber, J., Bongers, G., LeFevour, A., Buttini, M., & Mucke, L. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-12-05204.2002 · 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
Modulation of Alzheimer-like synaptic and cholinergic deficits in transgenic mice by human apolipoprotein E depends on isoform, aging, and overexpression of amyloid β peptides but not on plaque formation
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
Limited donepezil inhibition of acetylcholinesterase measured with positron emission tomography in living Alzheimer cerebral cortex
Kuhl, D. E., Minoshima, S., Frey, K. A., Foster, N. L., Kilbourn, M. R., & Koeppe, R. A. (2000) · Annals of Neurology · doi:10.1002/1531-8249(200009)48:3 · 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
Human Apolipoprotein E2, E3, and E4 Isoform-Specific Transgenic Mice: Human-like Pattern of GlialandNeuronal Immunoreactivity in Central Nervous System Not Observed in Wild-Type Mice
Xu, P.-T., Schmechel, D., Rothrock-Christian, T., Burkhart, D. S., Qiu, H.-L., Popko, B., Sullivan, P., Maeda, N., Saunders, A. M., Roses, A. D., et al. (1996) · Neurobiology of Disease · doi:10.1006/nbdi.1996.0023 · Cited by 178 · see citing works
Specific Regional Transcription of Apolipoprotein E in Human Brain Neurons
Xu, P., Gilbert, J. R., Qiu, H.-L., Ervin, J. F., Rothrock‐Christian, T., Hulette, C., & Schmechel, D. E. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65305-9 · Cited by 177 · see citing works
Apolipoprotein E4 Potentiates Amyloid β Peptide-induced Lysosomal Leakage and Apoptosis in Neuronal Cells
Ji, Z.-S., Miranda, R. D., Newhouse, Y. M., Weisgraber, K. H., Huang, Y., & Mahley, R. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m112109200 · Cited by 177 · see citing works
Self-citation
Targeting of Hepatitis C Virus Core Protein to Mitochondria through a Novel C-Terminal Localization Motif
Schwer, B., Ren, S., Pietschmann, T., Kartenbeck, J., Kaehlcke, K., Bartenschlager, R. F. W., Yen, T. S. B., & Ott, M. (2004) · Journal of Virology · doi:10.1128/jvi.78.15.7958-7968.2004 · Cited by 171 · see citing works
Emerging classes of protein–protein interaction inhibitors and new tools for their development
Pagliaro, L., Felding, J., Audouze, K., Nielsen, S. J., Terry, R. B., Krog-Jensen, C., & Butcher, S. (2004) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2004.06.006 · Cited by 168 · see citing works
Interdomain Communication in Hepatitis C Virus Polymerase Abolished by Small Molecule Inhibitors Bound to a Novel Allosteric Site
Marco, S. D., Volpari, C., Tomei, L., Altamura, S., Harper, S., Narjes, F., Koch, U., Rowley, M., Francesco, R. D., Migliaccio, G., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505423200 · Cited by 165 · see citing works
Truncated apolipoprotein E (ApoE) causes increased intracellular calcium and may mediate ApoE neurotoxicity
Tolar, M., Keller, J. N., Chan, S., Mattson, M. P., Marques, M. A., & Crutcher, K. A. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-16-07100.1999 · Cited by 148 · see citing works
Noninvasive intracellular delivery of functional peptides and proteins
Hawiger, J. (1999) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(99)80016-7 · Cited by 147 · see citing works
Prominent Axonopathy and Disruption of Axonal Transport in Transgenic Mice Expressing Human Apolipoprotein E4 in Neurons of Brain and Spinal Cord
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
Astroglial Regulation of Apolipoprotein E Expression in Neuronal Cells
Harris, F. M., Tesseur, I., Brecht, W. J., Xu, Q., Mullendorff, K., Chang, S., Wyss-Coray, T., Mahley, R. W., & Huang, Y. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309475200 · Cited by 135 · see citing works
Self-citation
Apolipoprotein E modulates Alzheimer’s Aβ(1–42)-induced oxidative damage to synaptosomes in an allele-specific manner
Lauderback, C. M., Kański, J., Hackett, J. M., Maeda, N., Kindy, M. S., & Butterfield, D. A. (2002) · Brain Research · doi:10.1016/s0006-8993(01)03228-0 · Cited by 132 · see citing works
Reactivity of Apolipoprotein E4 and Amyloid β Peptide
Ji, Z.-S., Müllendorff, K., Cheng, I. H., Miranda, R. D., Huang, Y., & Mahley, R. W. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m506646200 · Cited by 127 · see citing works
Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-analysis
Farrer, L. A. (1997) · JAMA · doi:10.1001/jama.1997.03550160069041 · Cited by 124 · see citing works
ApoE isoform affects LTP in human targeted replacement mice
Trommer, B. L., Shah, C., Yun, S. H., Gamkrelidze, G., Pasternak, E. S., Ye, G. L., Sotak, M., Sullivan, P. M., Pasternak, J. F., & LaDu, M. J. (2004) · NeuroReport · doi:10.1097/00001756-200412030-00020 · Cited by 124 · see citing works
A Minimally Lipidated Form of Cell-derived Apolipoprotein E Exhibits Isoform-specific Stimulation of Neurite Outgrowth in the Absence of Exogenous Lipids or Lipoproteins
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
Neurotoxicity of the 22 kDa Thrombin-Cleavage Fragment of Apolipoprotein E and Related Synthetic Peptides Is Receptor-Mediated
Tolar, M., Marques, M. A., Harmony, J. A. K., & Crutcher, K. A. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-15-05678.1997 · Cited by 115 · see citing works
Apolipoprotein E Expression by Neurons Surviving Excitotoxic Stress
Boschert, U., Merlo‐Pich, E., Higgins, G. A., Roses, A. D., & Catsicas, S. (1999) · Neurobiology of Disease · doi:10.1006/nbdi.1999.0251 · Cited by 110 · 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
Fluctuations caught in the act
Nielsen, L. K., Bjørnholm, T., & Mouritsen, O. G. (2000) · Nature · doi:10.1038/35006162 · Cited by 102 · see citing works
Association of APOE ε4 allele with survival in amyotrophic lateral sclerosis
Drory, V. E., Birnbaum, M., Korczyn, A. D., & Chapman, J. (2001) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(01)00569-x · Cited by 100 · see citing works
Mitochondrial protein import: two membranes, three translocases
Pfanner, N., & Wiedemann, N. (2002) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(02)00355-1 · Cited by 99 · see citing works
Dominant negative effects of apolipoprotein E4 revealed in transgenic models of neurodegenerative disease
Buttini, M., Akeefe, H., Lin, C. J., Mahley, R. W., Pitas, R. E., Wyss‐Coray, T., & Mucke, L. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00069-5 · Cited by 98 · see citing works
Self-citation
A thrombin cleavage fragment of apolipoprotein E exhibits isoform-specific neurotoxicity
Marques, M. A., Tolar, M., Harmony, J. A. K., & Crutcher, K. A. (1996) · Neuroreport · doi:10.1097/00001756-199611040-00025 · 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
Neuronal nicotinic acetylcholine receptor expression by O2A/oligodendrocyte progenitor cells
Rogers, S. W., Gregori, N. Z., Carlson, N. G., Gahring, L. C., & Noble, M. (2001) · Glia · doi:10.1002/1098-1136(20010315)33:4 · Cited by 94 · see citing works
Neurons of the Human Frontal Cortex Display Apolipoprotein E Immunoreactivity
Metzger, R. E., LaDu, M. J., Pan, J. B., Getz, G. S., Frail, D. E., & Falduto, M. T. (1996) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199603000-00013 · Cited by 94 · see citing works
Apolipoprotein E affects the amount, form, and anatomical distribution of amyloid β-peptide deposition in homozygous APP V717F transgenic mice
Irizarry, M. C., Cheung, B. S., Rebeck, G. W., Paul, S. M., Bales, K. R., & Hyman, B. T. (2000) · Acta Neuropathologica · doi:10.1007/s004010000263 · Cited by 93 · see citing works
Apolipoprotein E, Plaques, Tangles and Cholinergic Dysfunction in Alzheimer's Diseasea
Beffert, U., & Poirier, J. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb34415.x · Cited by 93 · see citing works
Modulation of Apolipoprotein E Structure by Domain Interaction
Hatters, D. M., Budamagunta, M. S., Voss, J. C., & Weisgraber, K. H. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506044200 · Cited by 88 · see citing works
Self-citation
Association of apolipoprotein E &#x26;isin;4 allele with bulbar-onset motor neuron disease
Al-Chalabi, A., Bakker, M. C., Shaw, C. E., Lloyd, C. M., Enayat, Z. E., Leigh, P. N., Sham, P. S., Ball, D. M., & Powell, J. F. (1996) · The Lancet · doi:10.1016/s0140-6736(96)90343-8 · Cited by 85 · see citing works
Apolipoprotein E4 Domain Interaction Occurs in Living Neuronal Cells as Determined by Fluorescence Resonance Energy Transfer
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-citation
Nerve Regeneration Occurs in the Absence of Apolipoprotein E in Mice
Popko, B., Goodrum, J. F., Bouldin, T. W., Zhang, S. H., & Maeda, N. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03268.x · Cited by 80 · see citing works
APOE: A potential marker of disease progression in ALS
Lacomblez, L., Doppler, V., Beucler, I., Costes, G., Salachas, F., Raisonnier, A., Forestier, N. L., Pradat, P., Bruckert, É., & Meininger, V. (2002) · Neurology · doi:10.1212/wnl.58.7.1112 · Cited by 79 · see citing works
Apolipoprotein E-epsilon 2 and Alzheimer's disease
Lippa, C. F., Smith, T. W., Saunders, A. M., Hulette, C., Pulaski-Salo, D., & Roses, A. D. (1997) · Neurology · doi:10.1212/wnl.48.2.515 · Cited by 77 · see citing works
Apolipoprotein E genotyping in sporadic amyotrophic lateral sclerosis: evidence for a major influence on the clinical presentation and prognosis
Moulard, B., Sefiani, A., Laamri, A., Malafosse, A., & Camu, W. (1996) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(96)00085-8 · Cited by 75 · 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
Transgenic mouse expressing human mutant α-galactosidase A in an endogenous enzyme deficient background: a biochemical animal model for studying active-site specific chaperone therapy for Fabry disease
Ishii, S., Yoshioka, H., Mannen, K., et al. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.07.001 · Cited by 74 · see citing works
Familial Dementia With Lewy Bodies
Tsuang, D. W., Dalan, A. M., Eugenio, C. J., Poorkaj, P., Limprasert, P., Spada, A. R. L., Steinbart, E. J., Bird, T. D., & Leverenz, J. B. (2002) · Archives of Neurology · doi:10.1001/archneur.59.10.1622 · Cited by 67 · see citing works
Kinetic Stabilization of an Oligomeric Protein under Physiological Conditions Demonstrated by a Lack of Subunit Exchange: Implications for Transthyretin Amyloidosis
Wiseman, R. L., Green, N. S., & Kelly, J. W. (2005) · Biochemistry · doi:10.1021/bi050352o · Cited by 65 · see citing works
Influence of Apolipoprotein E Genotype on Neuronal Damage and ApoE Immunoreactivity in Human Hippocampus Following Global Ischemia
Horsburgh, K. J., Graham, D. I., Stewart, J., & Nicoll, J. A. R. (1999) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199903000-00002 · Cited by 64 · see citing works
Herpes Simplex Virus Tegument Protein VP22 Contains Overlapping Domains for Cytoplasmic Localization, Microtubule Interaction, and Chromatin Binding
Martin, A. C. B. M., O’Hare, P., McLauchlan, J., et al. (2002) · Journal of Virology · doi:10.1128/jvi.76.10.4961-4970.2002 · Cited by 63 · see citing works
Familial Alzheimer Disease Among Caribbean Hispanics
Romas, S. N., Santana, V., Williamson, J., Ciappa, A., Lee, J. H., Rondon, H. Z., Estevez, P., Lantigua, R., Medrano, M. Z., Veras, M. A. T., et al. (2002) · Archives of Neurology · doi:10.1001/archneur.59.1.87 · Cited by 56 · see citing works
Chylomicron remnant metabolism. Role of hepatic lipoprotein receptors in mediating uptake.
Mahley, R. W., Hui, D. Y., Innerarity, T. L., et al. (1989) · PubMed · Cited by 54 · see citing works
Self-citation
Regionally specific neuronal expression of human APOE gene in transgenic mice
Xu, P., Gilbert, J. R., Qiu, H.-L., Rothrock‐Christian, T., Settles, D. L., Roses, A. D., & Schmechel, D. E. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00247-x · Cited by 50 · see citing works
Sialylated Human Apolipoprotein E (apoEs) Is Preferentially Associated with Neuron-Enriched Cultures from APOE Transgenic Mice
Xu, P., Schmechel, D. E., Qiu, H.-L., Herbstreith, M. H., Rothrock‐Christian, T., Eyster, M. V., Roses, A. D., & Gilbert, J. R. (1999) · Neurobiology of Disease · doi:10.1006/nbdi.1998.0213 · Cited by 46 · see citing works
ApoE Synthesis in Human Neuroblastoma Cells
Dupont-Wallois, L., Soulié, C., Sergeant, N., Wrieze, N. W.-D., Chartier‐Harlin, M., Delacourte, A., & Caillet‐Boudin, M. (1997) · Neurobiology of Disease · doi:10.1006/nbdi.1997.0155 · Cited by 45 · see citing works
Peripheral Sensory Nerve Defects in Apolipoprotein E Knockout Mice
Fullerton, S. M., Strittmatter, W. J., & Matthew, W. D. (1998) · Experimental Neurology · doi:10.1006/exnr.1998.6872 · Cited by 44 · see citing works
Expression of apolipoprotein E in normal and diverse neurodegenerative disease brain
Bao, F., Arai, H., Matsushita, S., Higuchi, S., & Sasaki, H. (1996) · Neuroreport · doi:10.1097/00001756-199607290-00008 · Cited by 44 · see citing works
Mapping of herpes simplex virus-1 VP22 functional domains for inter- and subcellular protein targeting
Aints, A., Guvén, H., Gahrton, G., et al. (2001) · Gene Therapy · doi:10.1038/sj.gt.3301493 · Cited by 40 · see citing works
The intracellular fate of apolipoprotein E is tau dependent and apoe allelespecific
Lovestone, S., Anderton, B. H., Hartley, C., Jensen, T. G., & Jørgensen, A. L. (1996) · Neuroreport · doi:10.1097/00001756-199604100-00010 · Cited by 35 · see citing works
APOE genotype is a risk factor for neuropathy severity in diabetic patients
Bedlack, R., Edelman, D. E., Gibbs, J., et al. (2003) · Neurology · doi:10.1212/01.wnl.0000056689.50682.94 · Cited by 34 · see citing works
APOE genotyping in differential diagnosis of Alzheimer's disease
Slooter, A. J. C., Breteler, M. M. B., Ott, A., Broeckhoven, C. V., & van Duijn, C. M. (1996) · The Lancet · doi:10.1016/s0140-6736(05)64501-1 · Cited by 33 · 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
Mitochondrial Stop and Go: Signals That Regulate Organelle Movement
Reynolds, I. J., & Rintoul, G. L. (2004) · Science s STKE · doi:10.1126/stke.2512004pe46 · Cited by 29 · see citing works
Apolipoprotein E ɛ4 in bulbar-onset motor neuron disease
Smith, R. G., Haverkamp, L. J., Case, S., Appel, V., & Appel, S. H. (1996) · The Lancet · doi:10.1016/s0140-6736(05)64502-3 · Cited by 28 · see citing works
Synthesis and Regulation of Apolipoprotein E during the Differentiation of Human Neuronal Precursor NT2/D1 Cells into Postmitotic Neurons
Ferreira, S., Dupire, M.-J., Delacourte, A., Najïb, J., & Caillet‐Boudin, M. (2000) · Experimental Neurology · doi:10.1006/exnr.2000.7510 · Cited by 25 · see citing works
Oxidative protein damage in cells engaged in β-amyloidosis is related to apoE genotype
Mazur‐Kolecka, B., Frackowiak, J., Kowal, D., Krzeslowska, J., & Dickson, D. W. (2002) · Neuroreport · doi:10.1097/00001756-200203250-00021 · Cited by 22 · see citing works
Synthesis of apolipoprotein E (ApoE) mRNA by human neuronal-type SK N SH-SY 5Y cells and its regulation by nerve growth factor and ApoE
Soulié, C., Mitchell, V. A., Dupont-Wallois, L., Chartier‐Harlin, M., Beauvillain, J., Delacourte, A., & Caillet‐Boudin, M. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00167-6 · Cited by 21 · see citing works
Efficient Nuclear Delivery of Antisense Oligodeoxynucleotides and Selective Inhibition of CETP Expression by Apo E Peptide in a Human CETP–Stably Transfected CHO Cell Line
Liu, K., Ou, J., Saku, K., Jimi, S., Via, D. P., Sparrow, J. T., Zhang, B., Pownall, H. J., Smith, L. C., & Arakawa, K. (1999) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.19.9.2207 · Cited by 7 · see citing works
Commentary on “Perspective on a pathogenesis and treatment of Alzheimer's disease.” Apolipoprotein E and the mitochondrial metabolic hypothesis
Huang, Y., & Mahley, R. W. (2006) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2005.12.006 · Cited by 6 · see citing works
Self-citation
Transfer of Antisense Oligodeoxynucleotides Against Endothelin Receptors A and B Into Human Coronary Smooth Muscle Cells and Endothelial Cells by Apolipoprotein E Peptide. An in Vitro Study.
Miura, S.-I., Okamoto, T., Via, D. P., & Saku, K. (2002) · Circulation Journal · doi:10.1253/circj.66.1054 · Cited by 3 · see citing works

Flagged first, then by citations

Research works printed but not linked: 27

[20]Alberts, M. J., Graffagnino, C., McClenny, C., DeLong, D., Strittmatter, W., Saunders, A. M. & Roses, A. D. (1995) Lancet 346, 575.
[23]Tardiff, B. E., Newman, M. F., Saunders, A. M., Strittmatter, W. J., Blumenthal, J. A., White, W. D., Croughwell, N. D., Davis, R. D., Jr., Roses, A. D., Reves, J. G., et al. (1997) Ann. Thorac. Surg. 64, 715-720.
[35]Bedlack, R. S., Edelman, D., Gibbs, J. W., III, Kelling, D., Strittmatter, W., Saunders, A. M. & Morgenlander, J. (2003) Neurology 60, 1022-1024.
[42]Small, G. W., Ercoli, L. M., Silverman, D. H. S., Huang, S.-C., Komo, S., Bookheimer, S. Y., Lavretsky, H., Miller, K., Siddarth, P., Rasgon, N. L., et al. (2000) Proc. Natl. Acad. Sci. USA 97, 6037-6042.
[43]Reiman, E. M., Caselli, R. J., Chen, K., Alexander, G. E., Bandy, D. & Frost, J. (2001) Proc. Natl. Acad. Sci. USA 98, 3334-3339.
[44]Reiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D., Saunders, A. M. & Hardy, J. (2004) Proc. Natl. Acad. Sci. USA 101, 284-289.
[45]Risner, M. E., Saunders, A. M., Altman, J. F. B., Ormandy, G. C., Craft, S., Foley, I. M., Zvartau-Hind, M. E., Hosford, D. A. & Roses, A. D. (2006) Pharmacogenomics J. , epub ahead of print.
[47]Roses, A. D. & Saunders, A. M. (2006) Alzheimer's Dementia , in press.
[50]Holtzman, D. M., Pitas, R. E., Kilbridge, J., Nathan, B., Mahley, R. W., Bu, G. & Schwartz, A. L. (1995) Proc. Natl. Acad. Sci. USA 92, 9480-9484.
[56]Strittmatter, W. J., Weisgraber, K. H., Goedert, M., Saunders, A. M., Huang, D., Corder, E. H., Dong, L.-M., Jakes, R., Alberts, M. J., Gilbert, J. R., et al. (1994) Exp. Neurol. 125, 163-171.
[64]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) Proc. Natl. Acad. Sci. USA 97, 2892-2897.
[67]Huang, Y., Liu, X. Q., Wyss-Coray, T., Brecht, W. J., Sanan, D. A. & Mahley, R. W. (2001) Proc. Natl. Acad. Sci. USA 98, 8838-8843.
[69]Raber, J., Wong, D., Buttini, M., Orth, M., Bellosta, S., Pitas, R. E., Mahley, R. W. & Mucke, L. (1998) Proc. Natl. Acad. Sci. USA 95, 10914-10919.
[75]Bales, 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) Proc. Natl. Acad. Sci. USA 96, 15233-15238.
[88]Raffaı ¨, R. L., Dong, L.-M., Farese, R. V., Jr., & Weisgraber, K. H. (2001) Proc. Natl. Acad. Sci. USA 98, 11587-11591.
[91]Dobson, C. M. (2001) Philos. Trans. R. Soc. London B 356, 133-145.
[93]Elshourbagy, N. A., Liao, W. S., Mahley, R. W. & Taylor, J. M. (1985) Proc. Natl. Acad. Sci. USA 82, 203-207.
[94]Ignatius, M. J., Gebicke-Ha ¨rter, P. J., Skene, J. H. P., Schilling, J. W., Weisgraber, K. H., Mahley, R. W. & Shooter, E. M. (1986) Proc. Natl. Acad. Sci. USA 83, 1125-1129.
[102]Han, S.-H., Einstein, G., Weisgraber, K. H., Strittmatter, W. J., Saunders, A. M., Pericak-Vance, M., Roses, A. D. & Schmechel, D. E. (1994) J. Neuropathol. Exp. Neurol. 53, 535-544.
[109]Xu, P.-T., Schmechel, D., Rothrock-Christian, T., Burkhart, D. S., Qiu, H.-L., Popko, B., Sullivan, P., Maeda, N., Saunders, A. M., Roses, A. D., et al. (1996) Neurobiol. Dis. 3, 229-245.
[121]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) Proc. Natl. Acad. Sci. USA 90, 8098-8102.
[122]Sanan, D. A., Weisgraber, K. H., Russell, S. J., Mahley, R. W., Huang, D., Saunders, A., Schmechel, D., Wisniewski, T., Frangione, B., Roses, A. D., et al. (1994) J. Clin. Invest. 94, 860-869.
[125]Ye, S., Huang, Y., Mu ¨llendorff, K., Dong, L., Giedt, G., Meng, E. C., Cohen, F. E., Kuntz, I. D., Weisgraber, K. H. & Mahley, R. W. (2005) Proc. Natl. Acad. Sci. USA 102, 18700-18705.
[128]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) Proc. Natl. Acad. Sci. USA 100, 10966-10971.
[130]Chang, S., Ma, T. R., Miranda, R. D., Balestra, M. E., Mahley, R. W. & Huang, Y. (2005) Proc. Natl. Acad. Sci. USA 102, 18694-18699.
[139]Fawell, S., Seery, J., Daikh, Y., Moore, C., Chen, L. L., Pepinsky, B. & Barsoum, J. (1994) Proc. Natl. Acad. Sci. USA 91, 664-668.
[152]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) Proc. Natl. Acad. Sci. USA 91, 11183-11186.

Sorted by citations

Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.263 · Cited by 3,459 · see citing works
Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans
Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., et al. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.016 · Cited by 2,087 · see citing works
Amyloid Beta: Structure, Biology and Structure-Based Therapeutic Development
Chen, G.-F., Xu, T.-H., Yan, Y., Zhou, Y.-R., Jiang, Y., Melcher, K., & Xu, H. E. (2017) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.28 · Cited by 1,965 · 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-citation
Amyloid-β–induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks
Palop, J. J., & Mucke, L. (2010) · Nature Neuroscience · doi:10.1038/nn.2583 · Cited by 1,651 · see citing works
The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · 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
Review Article: Genetics of Alzheimer Disease
Bekris, L. M., Yu, C.-E., Bird, T. D., & Tsuang, D. W. (2010) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988710383571 · Cited by 1,029 · see citing works
Neurotoxicity of Amyloid -Protein: Synaptic and Network Dysfunction
Mucke, L., & Selkoe, D. J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006338 · Cited by 1,000 · see citing works
Apolipoprotein E: Structure and function in lipid metabolism, neurobiology, and Alzheimer’s diseases
Huang, Y., & Mahley, R. W. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.08.025 · Cited by 829 · see citing works
Self-citation
apoE 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
Calcium and neurodegeneration
Mattson, M. P. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00275.x · Cited by 751 · see citing works
The role of microglia in amyloid clearance from the AD brain
Lee, C. Y. D., & Landreth, G. E. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0433-4 · Cited by 701 · see citing works
Epilepsy and Cognitive Impairments in Alzheimer Disease
Palop, J. J. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.15 · Cited by 684 · see citing works
Age, APOE and sex: triad of risk of Alzheimer’s disease.
Riedel, B. C., Thompson, P. M., & Brinton, R. D. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.03.012 · Cited by 627 · see citing works
Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS
Mahley, R. W., Weisgraber, K. H., & Huang, Y. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r800069-jlr200 · Cited by 580 · see citing works
Self-citation
The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D
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
Central Nervous System Lipoproteins: ApoE and Regulation of Cholesterol Metabolism
Mahley, R. W. (2016) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.116.307023 · Cited by 516 · see citing works
Self-citation
Reelin, lipoprotein receptors and synaptic plasticity
Herz, J., & Chen, Y. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn2009 · Cited by 524 · see citing works
Biology and Genetics of Prions Causing Neurodegeneration
Prusiner, S. B. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155524 · Cited by 455 · see citing works
Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector
Wang, C., Najm, R., Xu, Q., Jeong, D.-E., Walker, D., Balestra, M. E., Yoon, S. Y., Yuan, H., Li, G., Miller, Z. A., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0004-z · Cited by 428 · see citing works
Self-citation
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-citation
ApoE4 reduces glutamate receptor function and synaptic plasticity by selectively impairing ApoE receptor recycling
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
APOE genotype-specific differences in the innate immune response
Vitek, M. P., Brown, C. M., & Colton, C. A. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.11.014 · Cited by 362 · see citing works
The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology
Doifode, T., Giridharan, V. V., Generoso, J. S., Bhatti, G., Collodel, A., Schulz, P. E., Forlenza, O. V., & Barichello, T. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2020.105314 · Cited by 347 · see citing works
Comprehensive review of mechanisms of pathogenesis involved in Alzheimer’s disease and potential therapeutic strategies
Sharma, P., Srivastava, P., Seth, A., Tripathi, P. N., Banerjee, A. G., & Shrivastava, S. K. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.12.006 · Cited by 331 · see citing works
Apolipoprotein E4 Causes Age- and Tau-Dependent Impairment of GABAergic Interneurons, Leading to Learning and Memory Deficits in Mice
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-citation
GABAergic Interneuron Dysfunction Impairs Hippocampal Neurogenesis in Adult Apolipoprotein E4 Knockin Mice
Li, 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-citation
HumanAPOEIsoform-Dependent Effects on Brain β-Amyloid Levels in PDAPP Transgenic Mice
Bales, K. R., Liu, F., Wu, S., Lin, S., Koger, D., DeLong, C., Hansen, J. C., Sullivan, P. M., & Paul, S. M. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.0887-09.2009 · Cited by 274 · see citing works
Epigenetic regulation in the pathophysiology of Alzheimer's disease
Chouliaras, L., Rutten, B. P. F., Kenis, G., Peerbooms, O., Visser, P. J., Verhey, F., van Os, J., Steinbusch, H. W. M., & van den Hove, D. L. A. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.01.002 · Cited by 262 · see citing works
APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease
Youmans, K. L., Tai, L. M., Nwabuisi-Heath, E., Jungbauer, L., Kanekiyo, T., Gan, M., Kim, J., Eimer, W. A., Estus, S., Rebeck, G. W., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.407957 · Cited by 259 · see citing works
Apolipoprotein E (APOE) genotype has dissociable effects on memory and attentional–executive network function in Alzheimer’s disease
Wolk, D. A., Dickerson, B. C., Initiative, T. A. D. N., Weiner, M., Aiello, M., Aisen, P., Albert, M. S., Alexander, G., Anderson, H. S., Anderson, K., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001412107 · Cited by 248 · see citing works
APOE and TREM2 regulate amyloid-responsive microglia in Alzheimer’s disease
Nguyen, A. T., Wang, K., Hu, G., Wang, X., Miao, Z., Azevedo, J. A., Suh, E., Van Deerlin, V. M., Choi, D., Roeder, K., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02200-3 · Cited by 241 · see citing works
Selective effect of age, Apo e4, and Alzheimer's disease on hippocampal subfields
Mueller, S. G., & Weiner, M. W. (2009) · Hippocampus · doi:10.1002/hipo.20614 · Cited by 248 · see citing works
Concerted changes in transcripts in the prefrontal cortex precede neuropathology in Alzheimer's disease
Bossers, K., Wirz, K. T. S., Meerhoff, G. F., Essing, A. H. W., van Dongen, J. W., Houba, P., Kruse, C. G., Verhaagen, J., & Swaab, D. F. (2010) · Brain · doi:10.1093/brain/awq258 · Cited by 230 · 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-citation
Dementia, stroke, and vascular risk factors; a review
Sahathevan, R., Brodtmann, A., & Donnan, G. A. (2012) · International Journal of Stroke · doi:10.1111/j.1747-4949.2011.00731.x · Cited by 230 · see citing works
A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system
Alterman, J. F., Godinho, B. M. D. C., Hassler, M. R., Ferguson, C. M., Echeverria, D., Sapp, E., Haraszti, R. A., Coles, A. H., Conroy, F., Miller, R., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0205-0 · Cited by 227 · see citing works
Dendritic Spine Pathology in Neurodegenerative Diseases
Herms, J., & Dorostkar, M. M. (2016) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044216 · Cited by 201 · see citing works
APOE and Alzheimer’s Disease: Evidence Mounts that Targeting APOE4 may Combat Alzheimer’s Pathogenesis
Uddin, M. S., Kabir, M. T., Al Mamun, A., Abdel-Daim, M. M., Barreto, G. E., & Ashraf, G. M. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1237-z · Cited by 212 · see citing works
Apolipoprotein E4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for Alzheimer disease
Chen, H.-K., Ji, Z.-S., Dodson, S. E., Miranda, R. D., Rosenblum, C. I., Reynolds, I. J., Freedman, S. B., Weisgraber, K. H., Huang, Y., & Mahley, R. W. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.151084 · Cited by 209 · see citing works
Self-citation
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 · see citing works
APOE2 enhances neuroprotection against Alzheimer’s disease through multiple molecular mechanisms
Conejero-Goldberg, C., Gomar, J. J., Bobes-Bascaran, T., Hyde, T. M., Kleinman, J. E., Herman, M. M., Chen, S., Davies, P., & Goldberg, T. E. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.194 · Cited by 199 · 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-citation
Neuronal ApoE upregulates MHC-I expression to drive selective neurodegeneration in Alzheimer’s disease
Zalocusky, K. A., Najm, R., Taubes, A. L., Hao, Y., Yoon, S. Y., Koutsodendris, N., Nelson, M. R., Rao, A., Bennett, D. A., Bant, J., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00851-3 · Cited by 189 · see citing works
Self-citation
The forgotten APOE allele: A review of the evidence and suggested mechanisms for the protective effect of APOE ɛ2
Suri, S., Heise, V., Trachtenberg, A. J., & Mackay, C. E. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.10.010 · Cited by 183 · 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
A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer’s disease
Pasqualetti, P., Bonomini, C., Dal Forno, G., Paulon, L., Sinforiani, E., Marra, C., Zanetti, O., & Maria Rossini, P. (2009) · Aging Clinical and Experimental Research · doi:10.1007/bf03325217 · Cited by 172 · 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-citation
Reducing Human Apolipoprotein E Levels Attenuates Age-Dependent Aβ Accumulation in Mutant Human Amyloid Precursor Protein Transgenic Mice
Bien-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-citation
Apolipoprotein E and cholesterol in aging and disease in the brain
de Chaves, E. P., Narayanaswami, V., Christoffersen, C., & Nielsen, L. B. (2008) · Future Lipidology · doi:10.2217/17460875.3.5.505 · Cited by 164 · see citing works
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
Gene-environment interactions in Alzheimer's disease: A potential path to precision medicine
Eid, A., Mhatre, I., & Richardson, J. R. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.03.005 · Cited by 164 · see citing works
Relationship between Exercise and Alzheimer’s Disease: A Narrative Literature Review
Meng, Q., Lin, M.-S., & Tzeng, I.-S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00131 · Cited by 158 · see citing works
Understanding the association of apolipoprotein E4 with Alzheimer disease: clues from its structure
Zhong, N., & Weisgraber, K. H. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.r800009200 · Cited by 159 · see citing works
Self-citation
Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies
Pires, M., & Rego, A. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24010778 · Cited by 157 · see citing works
Direct Transcriptional Effects of Apolipoprotein E
Theendakara, V., Peters-Libeu, C. A., Spilman, P., Poksay, K. S., Bredesen, D. E., & Rao, R. V. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.3562-15.2016 · Cited by 152 · see citing works
Design and Validation of Liposomal ApoE2 Gene Delivery System to Evade Blood–Brain Barrier for Effective Treatment of Alzheimer’s Disease
Arora, S., Layek, B., & Singh, J. (2021) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00461 · Cited by 149 · see citing works
n−3 Fatty acid proportions in plasma and cognitive performance in older adults
Dullemeijer, C., Durga, J., Brouwer, I. A., van de Rest, O., Kok, F. J., Brummer, R.-J. M., van Boxtel, M. P., & Verhoef, P. (2007) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.5.1479 · Cited by 148 · see citing works
A molecular pathway of neurodegeneration linking α-synuclein to ApoE and Aβ peptides
Gallardo, G., Schlüter, O. M., & Südhof, T. C. (2008) · Nature Neuroscience · doi:10.1038/nn2058 · Cited by 145 · see citing works
Why is the amyloid beta peptide of Alzheimer’s disease neurotoxic?
Rauk, A. (2008) · Dalton Transactions · doi:10.1039/b718601k · Cited by 139 · see citing works
Drug development for alzheimer’s disease: Microglia induced neuroinflammation as a target
Dong, Y., Li, X., Cheng, J., & Hou, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030558 · Cited by 136 · see citing works
Targeting PCSK9 for hypercholesterolemia
Norata, G. D., Tibolla, G., & Catapano, A. L. (2014) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011613-140025 · Cited by 127 · see citing works
The dendritic hypothesis for Alzheimer's disease pathophysiology
Cochran, J. N., Hall, A. M., & Roberson, E. D. (2014) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.12.004 · Cited by 114 · see citing works
Accumulation of intraneuronal Aβ correlates with ApoE4 genotype
Christensen, D. Z., Schneider-Axmann, T., Lucassen, P. J., Bayer, T. A., & Wirths, O. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0666-1 · Cited by 120 · see citing works
The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation
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-citation
Selective effect of Apo e4 on CA3 and dentate in normal aging and Alzheimer's disease using high resolution MRI at 4 T
Mueller, S. G., Schuff, N., Raptentsetsang, S., Elman, J., & Weiner, M. W. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.04.174 · Cited by 116 · see citing works
Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function
Orr, A. L., Kim, C., Jimenez-Morales, D., Newton, B. W., Johnson, J. R., Krogan, N. J., Swaney, D. L., & Mahley, R. W. (2019) · Journal of Alzheimer's Disease · doi:10.3233/jad-181184 · Cited by 103 · see citing works
Self-citation
Lipid metabolism in Alzheimer’s disease
Liu, Q., & Zhang, J. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-013-1410-3 · Cited by 101 · see citing works
Cellular Receptors of Amyloid β Oligomers (AβOs) in Alzheimer’s Disease
Mroczko, B., Groblewska, M., Litman-Zawadzka, A., Kornhuber, J., & Lewczuk, P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19071884 · Cited by 97 · see citing works
Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function
Mak, A. C. Y., Pullinger, C. R., Tang, L. F., Wong, J. S., Deo, R. C., Schwarz, J.-M., Gugliucci, A., Movsesyan, I., Ishida, B. Y., Chu, C., et al. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2014.2011 · Cited by 96 · see citing works
Vision function abnormalities in Alzheimer disease
Tzekov, R., & Mullan, M. (2014) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2013.10.002 · Cited by 94 · see citing works
Mechanism underlying apolipoprotein E (ApoE) isoform‐dependent lipid efflux from neural cells in culture
Minagawa, H., Gong, J., Jung, C., Watanabe, A., Lund‐Katz, S., Phillips, M. C., Saito, H., & Michikawa, M. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22073 · Cited by 90 · see citing works
Disrupted functional and structural networks in cognitively normal elderly subjects with the APOE ɛ4 allele
Chen, Y., Chen, K., Zhang, J., Li, X., Shu, N., Wang, J., Zhang, Z., & Reiman, E. M. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2014.302 · Cited by 67 · see citing works
Early and late onset Alzheimer’s disease patients have distinct patterns of white matter damage.
Canu, E., Frisoni, G. B., Agosta, F., Pievani, M., Bonetti, M., & Filippi, M. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.09.021 · Cited by 67 · see citing works
Anti-inflammatory and Immune Therapy for Alzheimers Disease: Current Status and Future Directions
Walker, D., & Lue, L.-F. (2007) · Current Neuropharmacology · doi:10.2174/157015907782793667 · Cited by 66 · see citing works
CSF tau is associated with impaired cortical plasticity, cognitive decline and astrocyte survival only in APOE4-positive Alzheimer’s disease
Koch, G., Di Lorenzo, F., Loizzo, S., Motta, C., Travaglione, S., Baiula, M., Rimondini, R., Ponzo, V., Bonnì, S., Toniolo, S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-14204-3 · Cited by 64 · see citing works
A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice
Wiesmann, M., Zerbi, V., Jansen, D., Haast, R., Lütjohann, D., Broersen, L. M., Heerschap, A., & Kiliaan, A. J. (2016) · Neural Plasticity · doi:10.1155/2016/6846721 · Cited by 60 · see citing works
A New Hypothesis for Alzheimer’s Disease: The Lipid Invasion Model
Rudge, J. D. (2022) · Journal of Alzheimer's Disease Reports · doi:10.3233/adr-210299 · Cited by 58 · see citing works
Alzheimer disease and the periodontal patient: New insights, connections, and therapies
Ryder, M. I., & Xenoudi, P. (2021) · Periodontology 2000 · doi:10.1111/prd.12389 · Cited by 55 · see citing works
Apolipoprotein E as a β-amyloid-independent factor in Alzheimer’s disease
Wolf, A. B., Valla, J., Bu, G., Kim, J., LaDu, M., Reiman, E. M., & Caselli, R. J. (2013) · Alzheimer's Research & Therapy · doi:10.1186/alzrt204 · Cited by 55 · see citing works
Apolipoprotein E: Remarkable Protein Sheds Light on Cardiovascular and Neurological Diseases
Mahley, R. W. (2017) · Clinical Chemistry · doi:10.1373/clinchem.2016.255695 · Cited by 53 · see citing works
Self-citation
TOMM40 rs10524523 polymorphism's role in late-onset Alzheimer's disease and in longevity
Maruszak, A., Pepłońska, B., Safranow, K., Chodakowska-Żebrowska, M., Barcikowska, M., & Żekanowski, C. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110743 · Cited by 50 · see citing works
Sex-Specific Cross Tissue Meta-Analysis Identifies Immune Dysregulation in Women With Alzheimer’s Disease
Paranjpe, M. D., Belonwu, S., Wang, J. K., Oskotsky, T., Gupta, A., Taubes, A., Zalocusky, K. A., Paranjpe, I., Glicksberg, B. S., Huang, Y., et al. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.735611 · Cited by 49 · see citing works
Self-citation
Prediction of fast decline in amyloid positive mild cognitive impairment patients using multimodal biomarkers
Jang, H., Park, J., Woo, S., Kim, S., Kim, H. J., Na, D. L., Lockhart, S. N., Kim, Y., Kim, K. W., Cho, S. H., et al. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2019.101941 · Cited by 46 · see citing works
HtrA1 Proteolysis of ApoE In Vitro Is Allele Selective
Chu, Q., Diedrich, J. K., Vaughan, J. M., Donaldson, C. J., Nunn, M. F., Lee, K.-F., & Saghatelian, A. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b03463 · Cited by 46 · see citing works
An apolipoprotein E4 fragment can promote intracellular accumulation of amyloid peptide beta 42
Dafnis, I., Stratikos, E., Tzinia, A., Tsilibary, E. C., Zannis, V. I., & Chroni, A. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06756.x · Cited by 41 · see citing works
Ten years of proteomics in multiple sclerosis
Farias, A. S., Pradella, F., Schmitt, A., Santos, L. M. B., & Martins‐de‐Souza, D. (2014) · PROTEOMICS · doi:10.1002/pmic.201300268 · Cited by 40 · see citing works
Apolipoprotein E ε4-related thickening of the cerebral cortex modulates selective attention
Espeseth, T., Westlye, L. T., Walhovd, K. B., Fjell, A. M., Endestad, T., Rootwelt, H., & Reinvang, I. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.12.027 · Cited by 32 · see citing works
The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway
Naguib, S., Lopez-Lee, C., Torres, E. R., Lee, S.-I., Zhu, J., Zhu, D., Ye, P., Norman, K., Zhao, M., Wong, M. Y., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.05.023 · Cited by 32 · see citing works
Molecular Basis for Increased Risk for Late-onset Alzheimer Disease Due to the Naturally Occurring L28P Mutation in Apolipoprotein E4
Argyri, L., Dafnis, I., Theodossiou, T. A., Gantz, D., Stratikos, E., & Chroni, A. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.538124 · Cited by 30 · see citing works
Alzheimer’s Disease and Herbal Combination Therapy: A Comprehensive Review
Pradeep, S., Jain, A. S., Dharmashekara, C., Prasad, S. K., Kollur, S. P., Syed, A., & Shivamallu, C. (2020) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-200228 · Cited by 30 · see citing works
APOE3 - R136S mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition
Naguib, S., Lopez-Lee, C., Torres, E. R., Lee, S.-I., Zhu, J., Zhu, D., Ye, P., Norman, K., Zhao, M., Wong, M. Y., et al. (2024) · doi:10.1101/2024.04.25.591140 · Cited by 25 · see citing works
Biophysical Analysis of Apolipoprotein E3 Variants Linked with Development of Type III Hyperlipoproteinemia
Georgiadou, D., Chroni, A., Vezeridis, A., Zannis, V. I., & Stratikos, E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027037 · Cited by 24 · see citing works
A neuronal VLDLR variant lacking the third complement-type repeat exhibits high capacity binding of apoE containing lipoproteins
Sakai, K., Tiebel, O., Ljungberg, M. C., Sullivan, M., Lee, H.-J., Terashima, T., Li, R., Kobayashi, K., Lu, H.-C., Chan, L., et al. (2009) · Brain Research · doi:10.1016/j.brainres.2009.04.030 · Cited by 23 · see citing works
Molecular etiology of a dominant form of type III hyperlipoproteinemia caused by R142C substitution in apoE4
Vezeridis, A. M., Drosatos, K., & Zannis, V. I. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m008409 · Cited by 11 · see citing works
apoE3[K146N/R147W] acts as a dominant negative apoE form that prevents remnant clearance and inhibits the biogenesis of HDL
Fotakis, P., Vezeridis, A., Dafnis, I., Chroni, A., Kardassis, D., & Zannis, V. I. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m048348 · Cited by 4 · see citing works

Deciphering the contributions of neuroinflammation to neurodegeneration: lessons from antibody-mediated encephalitis and coronavirus disease 2019
Shir, D., & Day, G. S. (2022) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001033 · Cited by 13 · see citing works
Recent advances in the mechanisms of neuroinflammation and their roles in neurodegeneration
Niranjan, R. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2018.07.003 · Cited by 112 · see citing works
Mitochondria and the Link Between Neuroinflammation and Neurodegeneration
Filippo, M. D., Chiasserini, D., Tozzi, A., Picconi, B., & Calabresi, P. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100543 · Cited by 158 · see citing works
Lipopolysaccharide-induced neuroinflammation as a bridge to understand neurodegeneration
Batista, C. R. A., Gomes, G. F., Candelario-Jalil, E., Fiebich, B. L., & de Oliveira, A. C. P. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092293 · Cited by 529 · see citing works
IFNγ drives neuroinflammation, demyelination, and neurodegeneration in a mouse model of multiple system atrophy
Corbin-Stein, N. J., Childers, G. M., Webster, J. M., Zane, A., Yang, Y.-T., Mudium, N., Gupta, R. K., Manfredsson, F., Kordower, J., & Harms, A. (2024) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01710-x · Cited by 20 · see citing works

Authors: Mahley, R. W., Weisgraber, K. H., & Huang, Y.
Affiliations: Gladstone Institutes (US)
ORCID: Mahley, Robert W.
Huang, Yadong
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2006-04-11
Volume: 103
Issue: 15
Pages: 5644-5651
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0600549103
PMC: PMC1414631
OpenAlex: W2061916198
Cited by: 912
References: 166
Citations by year: 2026: 11 · 2025: 20 · 2024: 33 · 2023: 27 · 2022: 36 · 2021: 38 · 2020: 38 · 2019: 41 · 2018: 28 · 2017: 44 · 2016: 44 · 2015: 49 · 2014: 50 · 2013: 69 · 2012: 62
FWCI: 7.30
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (AG‐022074)
National Institute on Aging (P01AG022074)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords: APOE ε4, Alzheimer's disease, neuropathology, lipid homeostasis, amyloid-beta, oxidative stress, ischemia, neuroinflammation, traumatic brain injury, molten globule, cytoskeleton disruption, protease inhibitors, therapeutic target
MeSH terms: Alzheimer Disease, Apolipoproteins E, Humans, Lysosomes, Models, Neurological, Nervous System Diseases, Risk Factors, Amyloid beta-Peptides, Apoptosis, Apolipoprotein E4

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

Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer’s disease

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks