The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Open accessAbstract
Apolipoprotein E, type epsilon 4 allele (APOE epsilon 4), is associated with late-onset familial Alzheimer's disease (AD). There is high avidity and specific binding of amyloid beta-peptide with the protein ApoE. To test the hypothesis that late-onset familial AD may represent the clustering of sporadic AD in families large enough to be studied, we extended the analyses of APOE alleles to several series of sporadic AD patients. APOE epsilon 4 is significantly associated with a series of probable sporadic AD patients (0.36 +/- 0.042, AD, versus 0.16 +/- 0.027, controls [allele frequency estimate +/- standard error], p = 0.00031). Spouse controls did not differ from CEPH grandparent controls from the Centre d'Etude du Polymorphisme Humain (CEPH) or from literature controls. A large combined series of autopsy-documented sporadic AD patients also demonstrated highly significant association with the APOE epsilon 4 allele (0.40 +/- 0.026, p < or = 0.00001). These data support the involvement of ApoE epsilon 4 in the pathogenesis of late-onset familial and sporadic AD. ApoE isoforms may play an important role in the metabolism of beta-peptide, and APOE epsilon 4 may operate as a susceptibility gene (risk factor) for the clinical expression of AD.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The greatest risk factors for late-onset Alzheimer's are older age, 62,63 genetics 64,65 -especially the e4 form of the apolipoprotein E (APOE) gene -and having a family history of Alzheimer's.[66][67][68][69]”
From 2023 Alzheimer's disease facts and figures (2023) · cites this paper as [64]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Between 45% and 50% of AD patients carry at least one APOE4 allele compared to only 15% of age-matched healthy controls.5,11”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The major risk factor for AD is inheritance of the E4 allele of apolipoprotein E (APOE).5,6”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset, sporadic Alzheimer’s disease (AD).”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the presence of which dramatically increases risk for developing AD and decreases age of onset by 10 to 15 years”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [3]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Variables available from the CCSMA included age of dementia onset, gender, education, and presence of one or two APOE ε4 alleles, determined from buccal DNA.(24)”
From Progression of Cognitive, Functional, and Neuropsychiatric Symptom Domains in a Population Cohort With Alzheimer Dementia: The Cache County Dementia Progression Study (2011) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Among these genes, apolipoprotein E ( APOE ; especially the APOE ε 4 allele) is the highest genetic risk factor for LOAD [23,24].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [23]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The three primary APOE isoforms (APOE2, APOE3, and APOE4) have distinct effects on AD onset and age-related progression, with APOE4 increasing susceptibility and APOE2 offering protection (Corder et al., 1993; Saunders et al., 1993; Wolf et al., 2013).”
From Isogenic human stem cell models reveal mutation-dependent protective mechanisms of APOE3 Christchurch (2026) · cites this paper as Saunders et al., 1993
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the ε4 allele is the strongest genetic risk factor for late-onset AD”
From ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease (2022) · cites this paper as Saunders et al 1993
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The risk for AD is 3–4-fold higher in individuals carrying one APOE ε4 allele and about 10–15-fold higher in those carrying two APOE ε4 alleles”
From ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease (2022) · cites this paper as Saunders et al 1993
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In conclusion, APOE4 is the strongest genetic risk factor for AD with high prevalence (Saunders et al 1993, Sims et al 2020).”
From ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease (2022) · cites this paper as Saunders et al 1993
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The ε-4 isoform of apoE is the strongest molecular risk factor for the development of AD. About 60–80% of AD patients have at least one copy of apoE4 [2], [4], [5] and the risk for AD is increased in an ε-4 allele dose-dependent manner [6].”
From LDLR Expression and Localization Are Altered in Mouse and Human Cell Culture Models of Alzheimer's Disease (2010) · cites this paper as [5]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The greatest risk factors for Alzheimer's dementia are older age, 70 , 71 genetics — especially the e4 form of the apolipoprotein E (APOE) gene 72 , 73 — and having a family history of Alzheimer's dementia.”
From 2024 Alzheimer's disease facts and figures (2024) · cites this paper as [72]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“in contrast, the APOE ε2 allele confers protection against developing AD (2-5).”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [3]
Experimental — accuracy not yet measuredIn the citing paper
“Variants of the apolipoprotein E allele appear to account for most cases of late-onset Alzheimer's disease”
From Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E (1996) · cites this paper as [3]
In the citing paper
“the e4 allele has been associated with an increased risk of Alzheimer's disease, 1-7”
From Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E (1996) · cites this paper as [3]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Molecular cloning: A laboratory manual
Deininger, P. L. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90595-z · Cited by 84,684
Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI.
Hixson, J., & Vernier, D. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)43176-1 · Cited by 2,933
Boneau, C. A., & Hays, W. L. (1966) · The American Journal of Psychology · doi:10.2307/1420739 · Cited by 1,887
The Genetic Defect Causing Familial Alzheimer's Disease Maps on Chromosome 21
George‐Hyslop, P. S., Tanzi, R. E., Polinsky, R. J., Haines, J. L., Nee, L. E., Watkins, P. C., Myers, R. H., Feldman, R. G., Pollen, D. A., Drachman, D. A., et al. (1987) · Science · doi:10.1126/science.2880399 · Cited by 1,160
Self-citationGenetic Linkage Evidence for a Familial Alzheimer's Disease Locus on Chromosome 14
Schellenberg, G. D., Bird, T. D., Wijsman, E. M., Orr, H. T., Anderson, L., Nemens, E. J., White, J. A., Bonnycastle, L. L., Weber, J. L., Alonso, M. E., et al. (1992) · Science · doi:10.1126/science.1411576 · Cited by 957
Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid
Wisniewski, T., & Frangione, B. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90444-c · Cited by 802
Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage.
(1991) · Europe PMC (PubMed Central) · Cited by 758
Centre d'Etude du polymorphisme humain (CEPH): Collaborative genetic mapping of the human genome
Dausset, J. B., Cann, H. M., Cohen, D., Lathrop, M. G., Lalouel, J.-M., & White, R. L. (1990) · Genomics · doi:10.1016/0888-7543(90)90491-c · Cited by 575
Hallman, D. M., Boerwinkle, E., Saha, N., Sandholzer, C., Menzel, H., Csazar, A., & Utermann, G. (1991) · PubMed · Cited by 511
American Medical Association Council on Scientific Affairs
Goodman, C. S. (1988) · Cited by 496
Research works printed but not linked: 27
- [1]1. Neurology 1989;39: 125-126.
- [5]5. Sheskin D. Statistical tests and experimental design: a case- book. New York: Gardner Press, 1984:23-24.
- [7]7. Jennett B, Plum F. Persistent vegetative state after brain damage: a syndrome in search of a name. Lancet 1972; 1:734-737.
- [8]8. New "Baby Doe" rules tested. Am Med News 1986;1:45.
- [9]9. Teasdale G, Jennett B. Assessment of coma and impaired consciousness: a practical scale. Lancet 1974;2:81-83.
- [10]10. Sazbon L. Prolonged coma. Prog Clin Neurosci 1985;2:65-81.
- [11]11. Sazbon L, Groswasser Z. Outcome in 134 patients with pro- longed posttraumatic unawareness. Part 1: parameters determining late recovery of consciousness. J Neurosurg 1990;72:75-80.
- [12]12. Bricolo A, Turazzi S, Feriotti G. Prolonged posttraumatic unconsciousness: therapeutic assets and liabilities. J Neuro- surg 1980;52:625-634.
- [14]14. Hagen C. Language disorders secondary t o closed head injury: diagnosis and treatment. Top Lang Dis 1981;1:73-87.
- [15]15. Alexander MP. Traumatic brain injury. In: Benson DF, Blumer D, eds. Psychiatric aspects of neurologic disease, vol. 2. New York: Grune & Stratton, 1982:219-247.
- [18]18. Lehman LB. The persistent vegetative state. Postgrad Med 1990;88: 150,152.
- [19]19. Berrol S. Considerations for management of the persistent vegetative state. Arch Phys Med Rehabil 1986;67:283-285. 1992;73:628-634. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12
- [21]21. Goate A, Chartier-Harlin MC, Mullan M, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature Naruse S, Igarashi S , Aoki K, et al. Mis-sense mutation Val bIle in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease. Lancet 1991;337:978- 979.
- [22]22. Chartier-Harlin M-C, Crawford F, Houlden H, et al. Early- onset Alzheimer's disease caused by mutations at codon 717 of t h e P-amyloid precursor protein gene. Nature Murrell J, Farlow M, Ghetti B, Benson MD. A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science 1991;254:97-99.
- [24]24. Karlinsky H, Vaula G, Haines JL, et al. Molecular and prospective phenotypic characterization of a pedigree with familial Alzheimer's disease and a missense mutation in codon 717 of t h e P-amyloid precursor protein gene. Neurology 1992;42:1445-1453.
- [25]25. Hendriks L, van Duijn CM, Cras P, et al. Presenile demen- tia and cerebral haemorrhage linked to a mutation at codon 692 of the P-amyloid precursor protein. Nature Genet Mullan M, Crawford F, Axelman K, e t al. A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of P-amyloid. Nature Genet 1992;1:345- 347.
- [29]29. S t r i t t m a t WJ, Saunders AM, Schmechel D, e t al. Apolipoprotein E: high affinity binding to PA amyloid and August 1993 NEUROLOGY 43 1471 1991;349:704-706. 1991;353:844-846. 19923 :218-221. increased frequency of type 4 allele in familial Alzheimer's. Proc Natl Acad Sci USA 1993;90:1977-1981.
- [30]30. Ropers HH, Pericak-Vance MA. Report o f the committee on the genetic constitution o f chromosome 19. Human Gene Mapping 11 (1991). Cytogenet Cell Genet 1991;58:751-784.
- [32]32. Namba Y, Tomonaga M, Kawasaki H, Otomo E, Ikeda K. Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeld-Jakob disease. Brain Res 1991;541:163-166.
- [35]35. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the aus- pices of Department o f Health and Human Services Task Force on Alzheimer's disease. Neurology 1984;34:939-944.
- [38]38. Pericak-Vance MA, Yamaoka LH, Assinder RIF, et al. Tight linkage of apolipoprotein C2 to myotonic dystrophy on chro- mosome 19. Neurology 1986;36: 1418-1423.
- [45]45. Lathrop GM, Lalouel JM. Easy calculations of lad scores and genetic risks on small computers. Am J Hum Genet 31. Lathrop GM, Lalouel JM, Julier C, Ott J . Strategies for mul- 1990;6:575-577. 1988;102:271-279. 1984;36:460-465. tilocus linkage analysis in humans. Proc Natl Acad Sci USA
- [47]47. Ehnholm C, Lukka M, Kuusi T, Nikkila E, Utermann G. Apolipoprotein E polymorphisms in Finland. In: Fidge NH, Nestel P J , eds. Excerpta medica: Atherosclerosis VII. Amsterdam: Elsevier, 1986:325-328.
- [48]48. Mahley RW, Rall SC. Type 111 hyperlipoproteinemia (dys- betalipoproteinemia): the role of apolipoprotein E in normal and abnormal lipoprotein metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic basis of inherited disease. 6 t h ed. New York: McGraw-Hill, 36.
- [52]52. Haass C, Schlossmacher MG, Hung AY, et al. Amyloid p- peptide i s produced by cultured cells during normal metabolism. Nature 1992;359:322-325.
- [53]53. Seubert P, Vigo-Pelfry C, Esch F, e t al. Isolation and quan- tification of soluble Alzheimer's @-peptide from biological flu- ids. Nature 1992;359:325-327.
- [57]57. Schmechel DE, Saunders AM, Strittmatter WJ, e t al. Increased amyloid P-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer's disease. Proc Natl Acad Sci USA (in press). 1984;81:3443-3446. 1983;3:310-315. 1989:1195-1213. 1988;78:244-247. 1985;82:203-207.
Cited by
Sorted by citations
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
Self-citationAlzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063
2016 Alzheimer's disease facts and figures
Alzheimer's Association (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.001 · Cited by 5,069
Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., et al. (1995) · Nature · doi:10.1038/375754a0 · Cited by 4,051
Self-citation2023 Alzheimer's disease facts and figures
(2023) · Alzheimer's & Dementia · doi:10.1002/alz.13016 · Cited by 3,212
Variant of TREM2 Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558
2024 Alzheimer's disease facts and figures
(2024) · Alzheimer's & Dementia · doi:10.1002/alz.13809 · Cited by 2,536
2019 Alzheimer’s disease facts and figures.
Alzheimer's Association (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2019.01.010 · Cited by 2,461
2020 Alzheimer's disease facts and figures
(2020) · Alzheimer's & Dementia · doi:10.1002/alz.12068 · Cited by 2,353
Oxidative stress hypothesis in Alzheimer’s disease
Markesbery, W. R. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00629-6 · Cited by 2,383
Inflammation as a central mechanism in Alzheimer's disease
Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.06.014 · Cited by 2,253
Initiative, T. A. D. N., Hollingworth, P., CHARGE consortium, EADI1 consortium, Harold, D., Sims, R., Gerrish, A., Lambert, J.-C., Carrasquillo, M. M., Abraham, R., et al. (2011) · Nature Genetics · doi:10.1038/ng.803 · Cited by 1,997
2018 Alzheimer's disease facts and figures
Alzheimer's Association (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.001 · Cited by 1,912
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
Self-citationPreclinical Alzheimer’s Disease: Definition, Natural History, and Diagnostic Criteria
Dubois, B., Hampel, H., Feldman, H. H., Scheltens, P., Aisen, P., Andrieu, S., Bakardjian, H., Benali, H., Bertram, L., Blennow, K., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.02.002 · Cited by 1,925
Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database
Bertram, L., McQueen, M. B., Mullin, K., Blacker, D., & Tanzi, R. E. (2007) · Nature Genetics · doi:10.1038/ng1934 · Cited by 1,857
Masters, C. L., Bateman, R., Blennow, K., Rowe, C. C., Sperling, R. A., & Cummings, J. L. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.56 · Cited by 1,853
Enriched environments, experience-dependent plasticity and disorders of the nervous system
Nithianantharajah, J., & Hannan, A. J. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1970 · Cited by 1,771
Baumgart, M., Snyder, H. M., Carrillo, M. C., Fazio, S., Kim, H., & Johns, H. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.05.016 · Cited by 1,660
Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report
Nelson, P. T., Dickson, D. W., Trojanowski, J. Q., Jack, C. R., Boyle, P. A., Arfanakis, K., Rademakers, R., Alafuzoff, I., Attems, J., Brayne, C., et al. (2019) · Brain · doi:10.1093/brain/awz099 · Cited by 1,547
Characterization of single-nucleotide polymorphisms in coding regions of human genes
Cargill, M., Altshuler, D., Ireland, J., Sklar, P., Ardlie, K., Patil, N., Lane, C. R., Lim, E. P., Kalyanaraman, N., Nemesh, J., et al. (1999) · Nature Genetics · doi:10.1038/10290 · Cited by 1,547
Schmechel, D. E., Saunders, A. M., Strittmatter, W. J., Crain, B. J., Hulette, C. M., Joo, S. H., Pericak-Vance, M. A., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.20.9649 · Cited by 1,525
Self-citationApolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C., & Bu, G. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0228-7 · Cited by 1,425
Reiman, E. M., Caselli, R. J., Yun, L. S., Chen, K., Bandy, D., Minoshima, S., Thibodeau, S. N., & Osborne, D. (1996) · New England Journal of Medicine · doi:10.1056/nejm199603213341202 · Cited by 1,366
Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease
Prinz, M., & Priller, J. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3722 · Cited by 1,329
Patterns of Brain Activation in People at Risk for Alzheimer's Disease
Bookheimer, S. Y., Strojwas, M. H., Cohen, M. S., Saunders, A. M., Pericak-Vance, M. A., Mazziotta, J. C., & Small, G. W. (2000) · New England Journal of Medicine · doi:10.1056/nejm200008173430701 · Cited by 1,328
Self-citationHuman ApoE isoforms differentially regulate brain amyloid-β peptide clearance
Castellano, J. M., Kim, J., Stewart, F. R., Jiang, H., DeMattos, R. B., Patterson, B. W., Fagan, A. M., Morris, J. C., Mawuenyega, K. G., Cruchaga, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002156 · Cited by 1,242
Deciphering the Molecular Basis of Memory Failure in Alzheimer's Disease
Walsh, D. M., & Selkoe, D. J. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.010 · Cited by 1,207
The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease
Rogaeva, E., Meng, Y., Lee, J. H., Gu, Y., Kawarai, T., Zou, F., Katayama, T., Baldwin, C. T., Cheng, R., Hasegawa, H., et al. (2007) · Nature Genetics · doi:10.1038/ng1943 · Cited by 1,167
Self-citationBrain Cholesterol: Long Secret Life Behind a Barrier
Björkhem, I., & Meaney, S. (2004) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000120374.59826.1b · Cited by 1,044
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
Self-citationYeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C., & Sheng, M. (2016) · Neuron · doi:10.1016/j.neuron.2016.06.015 · Cited by 943
Cogswell, J. P., Ward, J., Taylor, I. A., Waters, M., Shi, Y., Cannon, B., Kelnar, K., Kemppainen, J., Brown, D., Chen, C., et al. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14103 · Cited by 943
Mahley, R. W., Weisgraber, K. H., & Huang, Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600549103 · Cited by 912
Blood–brain barrier breakdown as a therapeutic target in traumatic brain injury
Shlosberg, D., Benifla, M., Kaufer, D., & Friedman, A. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.74 · Cited by 897
The genetic landscape of Alzheimer disease: clinical implications and perspectives
Van Cauwenberghe, C., Van Broeckhoven, C., & Sleegers, K. (2016) · Genetics in Medicine · doi:10.1038/gim.2015.117 · Cited by 863
Apolipoprotein E in Alzheimer’s disease and other neurological disorders
Verghese, P. B., Castellano, J. M., & Holtzman, D. M. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70325-2 · Cited by 857
Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases
Selkoe, D. J. (2004) · Nature Cell Biology · doi:10.1038/ncb1104-1054 · Cited by 863
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
Self-citationTang, M.-X. (1998) · JAMA · doi:10.1001/jama.279.10.751 · Cited by 771
Walking and Dementia in Physically Capable Elderly Men
Abbott, R. D. (2004) · JAMA · doi:10.1001/jama.292.12.1447 · Cited by 743
Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses
Bertram, L., & Tanzi, R. E. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2494 · Cited by 747
History and progress of hypotheses and clinical trials for Alzheimer’s disease
Liu, P.-P., Xie, Y., Meng, X.-Y., & Kang, J.-S. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0063-8 · Cited by 723
APOE and Alzheimer disease: a major gene with semi-dominant inheritance
Genin, E., Hannequin, D., Wallon, D., Sleegers, K., Hiltunen, M., Combarros, O., Bullido, M. J., Engelborghs, S., De Deyn, P., Berr, C., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.52 · Cited by 714
Reduction of β‐amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease
Motter, R., Vigo‐Pelfrey, C., Kholodenko, D., Barbour, R., Johnson‐Wood, K., Galasko, D., Chang, L., Miller, B., Clark, C., Green, R., et al. (1995) · Annals of Neurology · doi:10.1002/ana.410380413 · Cited by 701
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
Self-citationBerg, L., McKeel, D. W., Miller, J. P., Storandt, M., Rubin, E. H., Morris, J. C., Baty, J., Coats, M., Norton, J., Goate, A. M., et al. (1998) · Archives of Neurology · doi:10.1001/archneur.55.3.326 · Cited by 657
Self-citationAge, 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
Molecular genetics of early-onset Alzheimer’s disease revisited
Cacace, R., Sleegers, K., & Van Broeckhoven, C. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.01.012 · Cited by 617
Apolipoprotein E structure: insights into function
Hatters, D. M., Peters-Libeu, C. A., & Weisgraber, K. H. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.06.008 · Cited by 583
Liang, W. S., Reiman, E. M., Valla, J., Dunckley, T., Beach, T. G., Grover, A., Niedzielko, T. L., Schneider, L. E., Mastroeni, D., Caselli, R., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709259105 · Cited by 585
Self-citationCoon, K. D., Myers, A. J., Craig, D. W., Webster, J. A., Pearson, J. V., Lince, D. H., Zismann, V. L., Beach, T. G., Leung, D., Bryden, L., et al. (2007) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v68n0419 · Cited by 569
Traumatic brain injury and amyloid-β pathology: a link to Alzheimer's disease?
Johnson, V. E., Stewart, W., & Smith, D. H. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2808 · Cited by 587
Small, G. W. (1995) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1995.03520360056039 · Cited by 604
Plasma and Cerebrospinal Fluid Levels of Amyloid β Proteins 1-40 and 1-42 in Alzheimer Disease
Mehta, P. D., Pirttilä, T., Mehta, S. P., Sersen, E. A., Aisen, P. S., & Wisniewski, H. M. (2000) · Archives of Neurology · doi:10.1001/archneur.57.1.100 · Cited by 582
Sullivan, P. M., Mezdour, H., Aratani, Y., Knouff, C., Najib, J., Reddick, R. L., Quarfordt, S. H., & Maeda, N. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.29.17972 · Cited by 575
Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides
Koistinaho, M., Lin, S., Wu, X., Esterman, M., Koger, D., Hanson, J., Higgs, R., Liu, F., Malkani, S., Bales, K. R., et al. (2004) · Nature Medicine · doi:10.1038/nm1058 · Cited by 571
Utility of the Apolipoprotein E Genotype in the Diagnosis of Alzheimer's Disease
Mayeux, R., Saunders, A. M., Shea, S., Mirra, S., Evans, D., Roses, A. D., Hyman, B. T., Crain, B., Tang, M.-X., & Phelps, C. H. (1998) · New England Journal of Medicine · doi:10.1056/nejm199802193380804 · Cited by 547
Self-citationLinking Aβ and Tau in Late-Onset Alzheimer's Disease: A Dual Pathway Hypothesis
Small, S. A., & Duff, K. (2008) · Neuron · doi:10.1016/j.neuron.2008.11.007 · Cited by 546
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
Longitudinal Modeling of Age-Related Memory Decline and the APOE ε4 Effect
Caselli, R. J., Dueck, A. C., Osborne, D., Sabbagh, M. N., Connor, D. J., Ahern, G. L., Baxter, L. C., Rapcsak, S. Z., Shi, J., Woodruff, B. K., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0809437 · Cited by 528
Xu, Q., Bernardo, A., Walker, D., Kanegawa, T., Mahley, R. W., & Huang, Y. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.5476-05.2006 · Cited by 524
Bertram, L., Lange, C., Mullin, K., Parkinson, M., Hsiao, M., Hogan, M. F., Schjeide, B. M. M., Hooli, B., DiVito, J., Ionita, I., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.10.008 · Cited by 511
Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease
Li, H., Wetten, S., Li, L., St. Jean, P. L., Upmanyu, R., Surh, L., Hosford, D., Barnes, M. R., Briley, J. D., Borrie, M., et al. (2008) · Archives of Neurology · doi:10.1001/archneurol.2007.3 · Cited by 499
Self-citationApolipoprotein E, Dementia, and Cortical Deposition of β-Amyloid Protein
Polvikoski, T., Sulkava, R., Haltia, M., Kainulainen, K., Vuorio, A., Verkkoniemi, A., Niinistö, L., Halonen, P., & Kontula, K. (1995) · New England Journal of Medicine · doi:10.1056/nejm199511093331902 · Cited by 493
Apolipoprotein E ε4 allele is associated with deposition of amyloid β-protein following head injury
Nicoll, J. A. R., Roberts, G. W., & Graham, D. I. (1995) · Nature Medicine · doi:10.1038/nm0295-135 · Cited by 486
Microvascular injury and blood–brain barrier leakage in Alzheimer's disease
Zipser, B. D., Johanson, C. E., Gonzalez, L., Berzin, T. M., Tavares, R., Hulette, C. M., Vitek, M. P., Hovanesian, V., & Stopa, E. G. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.05.016 · Cited by 487
Self-citationStrittmatter, 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
Self-citationApolipoprotein E alleles, dyslipidemia, and coronary heart disease. The Framingham Offspring Study
Wilson, P. W. F. (1994) · JAMA · doi:10.1001/jama.1994.03520210050031 · Cited by 468
Klimentidis, Y. C., Raichlen, D. A., Bea, J., Garcia, D. O., Wineinger, N. E., Mandarino, L. J., Alexander, G. E., Chen, Z., & Going, S. B. (2018) · International Journal of Obesity · doi:10.1038/s41366-018-0120-3 · Cited by 403
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
Redox‐Active Metals, Oxidative Stress, and Alzheimer's Disease Pathology
HUANG, X., MOIR, R. D., TANZI, R. E., BUSH, A. I., & ROGERS, J. T. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1306.012 · Cited by 425
Kalmijn, S., Foley, D., White, L., Burchfiel, C. M., Curb, J. D., Petrovitch, H., Ross, G. W., Havlik, R. J., & Launer, L. J. (2000) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.20.10.2255 · Cited by 417
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
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
Self-citationBrecht, W. J., Harris, F. M., Chang, S., Tesseur, I., Yu, G.-Q., Xu, Q., Dee Fish, J., Wyss-Coray, T., Buttini, M., Mucke, L., et al. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4315-03.2004 · Cited by 403
Clusterin in Alzheimer’s Disease: Mechanisms, Genetics, and Lessons From Other Pathologies
Foster, E. M., Dangla-Valls, A., Lovestone, S., Ribe, E. M., & Buckley, N. J. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00164 · Cited by 381
Clinical and pathological correlates of apolipoprotein E ε4 in Alzheimer's disease
Gomez‐Isla, T., West, H. L., Rebeck, G. W., Harr, S. D., Growdon, J. H., Locascio, J. J., Perls, T. T., Lipsitz, L. A., & Hyman, B. T. (1996) · Annals of Neurology · doi:10.1002/ana.410390110 · Cited by 378
Iron Toxicity in Diseases of Aging: Alzheimer's Disease, Parkinson's Disease and Atherosclerosis
Altamura, S., & Muckenthaler, M. U. (2009) · Journal of Alzheimer's Disease · doi:10.3233/jad-2009-1010 · Cited by 369
fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease
Bondi, M. W., Houston, W. S., Eyler, L. T., & Brown, G. G. (2005) · Neurology · doi:10.1212/01.wnl.0000150885.00929.7e · Cited by 372
Myers, R. H., Schaefer, E. J., Wilson, P. W. F., D'Agostino, R., Ordovas, J. M., Espino, A., Au, R., White, R. F., Knoefel, J. E., Cobb, J. L., et al. (1996) · Neurology · doi:10.1212/wnl.46.3.673 · Cited by 346
Davis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4526 · Cited by 341
RetractedAPOE ε4: The most prevalent yet understudied risk factor for Alzheimer's disease
Michaelson, D. M. (2014) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.06.015 · Cited by 331
A4POE*4-associated Alzheimer's disease risk is modified by α1–antichymotrypsin polymorphism
Kamboh, M. I., Sanghera, D. K., Ferrell, R. E., & DeKosky, S. T. (1995) · Nature Genetics · doi:10.1038/ng0895-486 · Cited by 336
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
Coding variants in TREM2 increase risk for Alzheimer's disease
Jin, S. C., Benitez, B. A., Karch, C. M., Cooper, B., Skorupa, T., Carrell, D., Norton, J. B., Hsu, S., Harari, O., Cai, Y., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu277 · Cited by 314
Oblak, A. L., Lin, P. B., Kotredes, K. P., Pandey, R. S., Garceau, D., Williams, H. M., Uyar, A., O’Rourke, R., O’Rourke, S., Ingraham, C., et al. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.713726 · Cited by 325
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
Human Whole-Genome Shotgun Sequencing
Weber, J. L., & Myers, E. W. (1997) · Genome Research · doi:10.1101/gr.7.5.401 · Cited by 311
Liang, W. S., Dunckley, T., Beach, T. G., Grover, A., Mastroeni, D., Ramsey, K., Caselli, R. J., Kukull, W. A., McKeel, D., Morris, J. C., et al. (2008) · Physiological Genomics · doi:10.1152/physiolgenomics.00242.2007 · Cited by 309
Self-citationGenes associated with Alzheimer's disease: an overview and current status
Giri, M., Lü, Y., & Zhang, M. (2016) · Clinical Interventions in Aging · doi:10.2147/cia.s105769 · Cited by 311
Cholesterol in brain disease: Sometimes determinant and frequently implicated
Martín, M. G., Pfrieger, F., & Dotti, C. G. (2014) · The EMBO Reports · doi:10.15252/embr.201439225 · Cited by 304
Heme oxygenase-1 and neurodegeneration: expanding frontiers of engagement
Schipper, H. M., Song, W., Zukor, H., Hascalovici, J. R., & Zeligman, D. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06160.x · Cited by 298
Fagan, A. M., Watson, M., Parsadanian, M., Bales, K. R., Paul, S. M., & Holtzman, D. M. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2002.0483 · Cited by 290
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
Fernandez, C. G., Hamby, M. E., McReynolds, M. L., & Ray, W. J. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00014 · Cited by 277
Human APOE Isoform-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
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
TOKUDA, T., CALERO, M., MATSUBARA, E., VIDAL, R., KUMAR, A., PERMANNE, B., ZLOKOVIC, B., SMITH, J. D., LADU, M. J., ROSTAGNO, A., et al. (2000) · Biochemical Journal · doi:10.1042/bj3480359 · Cited by 272
Centeno, E. G. Z., Cimarosti, H., & Bithell, A. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0258-4 · Cited by 268
Metadata
- Authors
- 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., Hulette, C., Crain, B., Goldgaber, D., & Roses, A. D.
- Affiliations
- Duke University (US)
- Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto,...
- Venue
- Neurology
- Published
- 1993-08
- Volume
- 43
- Issue
- 8
- Pages
- 1467-1467
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W1999631936
- Cited by
- 3,786
- References
- 29
- Citations by year
- 2026: 46 · 2025: 67 · 2024: 96 · 2023: 75 · 2022: 83 · 2021: 107 · 2020: 101 · 2019: 89 · 2018: 93 · 2017: 74 · 2016: 86 · 2015: 93 · 2014: 102 · 2013: 95 · 2012: 119
- FWCI
- 105.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association
- American Health Assistance Foundation
- Medical Research Council Canada
- National Institutes of Health (MO1-RR-30)
- Medical Research Council
- National Institute on Aging (NIA AG05128, NIA AG 07922)
- National Institute of Neurological Disorders and Stroke
- National Center for Research Resources (M01 RR 30)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- apolipoprotein E, APOE ε4, Alzheimer's disease, sporadic Alzheimer's disease, genetic susceptibility, amyloid-beta, APOE isoforms, allele frequency, genetic association
- MeSH terms
- Aged, Alleles, Alzheimer Disease, Apolipoproteins E, Female, Gene Amplification, Gene Frequency, Humans, Male, Middle Aged, Mutation
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
