Apolipoprotein E, Dementia, and Cortical Deposition of β-Amyloid Protein

Polvikoski, Tuomo; Sulkava, Raimo; Haltia, Matti; Kainulainen, Katariina; Vuorio, Alpo; Verkkoniemi, Auli; Niinistö, Leena; Halonen, Pirjo; Kontula, Kimmo

doi:10.1056/nejm199511093331902

Cited by 493Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Apolipoprotein E, Dementia, and Cortical Deposition of β-Amyloid Protein

Polvikoski, Tuomo, Sulkava, Raimo, Haltia, Matti, Kainulainen, Katariina, Vuorio, Alpo, Verkkoniemi, Auli, Niinistö, Leena, Halonen, Pirjo +1 more·1995·New England Journal of Medicine

DOI 10.1056/nejm199511093331902

Open this paper in CoChat — free account

Abstract

BACKGROUND: The epsilon 4 allele of apolipoprotein E has been associated with an increased risk of late-onset Alzheimer's disease. In a cohort of elderly subjects we prospectively investigated the relation between the apolipoprotein E genotype, dementia, and the accumulation of beta-amyloid protein in the cerebral cortex. METHODS: Autopsy involving neuropathological analysis and DNA analysis of frozen blood samples were performed in 92 of 271 persons who were at least 85 years of age, who had been living in Vantaa, Finland, on April 1, 1991, and who had died between that time and the end of 1993. All subjects had been tested for dementia. Apolipoprotein E genotyping was done with a solid-phase minisequencing technique. The percentage of the cortex occupied by methenamine silver-stained plaques was used as an estimate of the extent of beta-amyloid protein deposition. RESULTS: The frequency of the epsilon 4 allele was significantly higher in the subjects with Alzheimer's disease than in the subjects without dementia (30 percent vs. 8 percent, P < 0.001). There was a greater accumulation of beta-amyloid protein in the brain and more neurofibrillary tangles in the subjects with the epsilon 4 allele than in those without it (P < 0.001). The deposition of beta-amyloid protein varied according to the genotype in both the subjects with dementia and those without dementia: it was lowest in those with the epsilon 2/epsilon 3 genotype, intermediate in those with the epsilon 3/epsilon 3 genotype, and highest in those with the epsilon 3/epsilon 4 genotype. A single subject had the epsilon 4/epsilon 4 genotype and had dementia. CONCLUSIONS: The epsilon 4 allele of apolipoprotein E is significantly associated with Alzheimer's disease. Even in elderly subjects without dementia, the apolipoprotein E genotype is related to the degree of deposition of beta-amyloid protein in the cerebral cortex.

Integrity signals

Registry

Crossref · 10.1056/nejm199511093331902

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

There is a strong positive correlation between the APOE ε4 allele and Aβ pathology in human AD brains, with the highest Aβ burden in homozygous APOE ε4 carriers.
“there is a strong positive correlation between the APOE ε4 allele and Aβ pathology in human AD brains with the highest Aβ burden found in homozygous APOE ε4 carriers”
From ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease (2022) · cites this paper as Polvikoski et al 1995
The e4 allele is associated with an increased risk of Alzheimer's disease.
“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 [6]
The e2 allele is associated with slower rates of beta-amyloid protein and neurofibrillary-tangle deposition.
“slower rates of b-amyloid protein and neurofibrillary-tangle deposition, 6,40”
From Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E (1996) · cites this paper as [6]

Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,841 · see citing works
Clinical diagnosis of Alzheimer's disease: Report of the NINCDS‐ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · 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
The Consortium to Establish a Registry for Alzheimer's Disease (CERAD): Part II. Standardization of the neuropathologic assessment of Alzheimer's disease
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · see citing works
Vascular dementia: Diagnostic criteria for research studies: Report of the NINDS‐AIREN International Workshop*
Román, G. C., Tatemichi, T. K., Erkinjuntti, T., Cummings, J. L., Masdeu, J. C., Garcia, J. H., Amaducci, L., Orgogozo, J.-M., Brun, A., Hofman, A., et al. (1993) · Neurology · doi:10.1212/wnl.43.2.250 · Cited by 4,921 · 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
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
Some new, simple and efficient stereological methods and their use in pathological research and diagnosis.
GUNDERSEN, H. J. G., BENDTSEN, T. F., KORBO, L., MARCUSSEN, N., MØLLER, A., NIELSEN, K., NYENGAARD, J. R., PAKKENBERG, B., SØRENSEN, F. B., VESTERBY, A., et al. (1988) · APMIS · doi:10.1111/j.1699-0463.1988.tb05320.x · Cited by 2,929 · 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
Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.
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 · 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
Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease
Namba, Y., Tomonaga, M., Kawasaki, H., Otomo, E., & Ikeda, K. (1991) · Brain Research · doi:10.1016/0006-8993(91)91092-f · Cited by 1,157 · see citing works
Apolipoprotein E polymorphism and Alzheimer's disease
Poirier, J., Bertrand, P., Poirier, J., Kogan, S., Gauthier, S., Poirier, J., Gauthier, S., Davignon, J., Bouthillier, D., & Davignon, J. (1993) · The Lancet · doi:10.1016/0140-6736(93)91705-q · Cited by 1,108 · see citing works
Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions
William Rebeck, G., Reiter, J. S., Strickland, D. K., & Hyman, B. T. (1993) · Neuron · doi:10.1016/0896-6273(93)90070-8 · Cited by 1,107 · see citing works
Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid
Wisniewski, T., & Frangione, B. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90444-c · Cited by 802 · see citing works
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
Apolipoprotein E ∈4 allele distributions in late-onset Alzheimer's disease and in other amyloid-forming diseases
Saunders, A. M., Roses, A. D., Pericak‐Vance, M. A., Dole, K. C., Strittmatter, W. J., Schmechel, D. E., Szymanski, M. H., McCown, N., Manwaring, M., Schmader, K. E., et al. (1993) · The Lancet · doi:10.1016/0140-6736(93)91709-u · Cited by 498 · 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
Apolipoprotein E polymorphism in health and disease
Utermann, G. (1987) · American Heart Journal · doi:10.1016/0002-8703(87)90610-7 · Cited by 389 · see citing works
APOLIPOPROTEIN-E GENOTYPE AND ALZHEIMERS-DISEASE
Hardy, J., Houlden, H., Collinge, J., Kennedy, A. M., Newman, S., Rossor, M. N., Lannfelt, L., Lilius, L., Winblad, B. G., Crook, R., et al. (1993) · UCL Discovery (University College London) · Cited by 286 · see citing works
Apolipoprotein E genotype and Alzheimer's disease
Noguchi, S., Murakami, K., Yamada, N., Payami, H., Kaye, J. A., Heston, L. L., Bird, T. D., & Schellenberg, G. D. (1993) · The Lancet · doi:10.1016/0140-6736(93)91728-5 · Cited by 285 · see citing works
Apolipoprotein E: Binding to Soluble Alzheimer′s β-Amyloid
Wısnıewskı, T., Golabek, A. A., Matsubara, E., Ghiso, J. A., & Frangione, B. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.1423 · Cited by 265 · see citing works
Protection against Alzheimer's disease with apoE ∈2
Talbot, C., Lendon, C., Craddock, N., Shears, S., Morris, J., & Goate, A. (1994) · The Lancet · doi:10.1016/s0140-6736(94)92557-7 · Cited by 225 · see citing works
Association of apolipoprotein E phenotypes with late onset Alzheimer's disease: population based study
Kuusisto, J., Koivisto, K. J., Kervinen, K., Mykkänen, L. M., Helkala, E.-L., Vanhanen, M., Hänninen, T., Pyörälä, K., Kesäniemi, Y. A., Riekkinen, P. J., et al. (1994) · BMJ · doi:10.1136/bmj.309.6955.636 · Cited by 207 · see citing works
Identification of individuals by analysis of biallelic DNA markers, using PCR and solid-phase minisequencing.
Syvänen, A. C., Sajantila, A., & Lukka, M. (1993) · PubMed · Cited by 199 · see citing works
Alzheimer's Disease, Apolipoprotein E4, and Gender
Payami, H. (1994) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1994.03510410028015 · Cited by 190 · see citing works
Aging and genetic variation of plasma apolipoproteins. Relative loss of the apolipoprotein E4 phenotype in centenarians.
Louhija, J., Miettinen, H. E., KONTULA, K. K., Tikkanen, M. J., Miettinen, T. A., & Tilvis, R. S. (1994) · Arteriosclerosis and Thrombosis A Journal of Vascular Biology · doi:10.1161/01.atv.14.7.1084 · Cited by 172 · see citing works
Self-citation
Alzheimer's Disease and Possible Gene Interaction
George‐Hyslop, P. S., McLachlan, D. C., Tsuda, T., Rogaev, E. I., Karlinsky, H., Lippa, C. F., & Pollen, D. A. (1994) · Science · doi:10.1126/science.8290965 · Cited by 132 · see citing works
APOE genotype does not modulate age of onset in families with chromosome 14 encoded Alzheimer's disease
Broeckhoven, C. V., Backhovens, H., Cruts, M., Martin, J. J., Crook, R., Houlden, H., & Hardy, J. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90385-9 · Cited by 126 · see citing works
Clinical application of apolipoprotein E genotyping to Alzheimer's disease
Roses, A., Strittmatter, W., Pericak-Vance, M., Corder, E., Saunders, A., & Schmechel, D. (1994) · The Lancet · doi:10.1016/s0140-6736(94)92960-2 · Cited by 125 · see citing works
Lack of association of apolipoprotein E allele ϵ4 with late‐onset Alzheimer's disease among Finnish centenarians
Sobel, E., Louhija, J., Sulkava, R. O., Davanipour, Z., KONTULA, K. K., Miettinen, H. E., Tikkanen, M., Kainulainen, K., & Tilvis, R. S. (1995) · Neurology · doi:10.1212/wnl.45.5.903 · Cited by 122 · see citing works
Self-citation
Distinctive, rapid, and easy labeling of diffuse plaques in the Alzheimer brains by a new methenamine silver stain
Yamaguchi, H., Haga, C., Hirai, S., Nakazato, Y., & Kosaka, K. (1990) · Acta Neuropathologica · doi:10.1007/bf00296119 · Cited by 86 · see citing works
EARLY SENILE PLAQUES IN DOWN'S SYNDROME BRAINS SHOW A CLOSE RELATIONSHIP WITH CELL BODIES OF NEURONS
Allsop, D., Haga, S., Haga, C., Ikeda, S., Mann, D. M. A., & Ishii, T. (1989) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1989.tb01252.x · Cited by 82 · see citing works
Apolipoprotein E Interaction with the Neurofibrillary Tangles and Senile Plaques in Alzheimer Disease: Implications for Disease Pathogenesis
Richey, P. L., Siedlak, S. L., Smith, M. A., & Perry, G. L. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.1389 · Cited by 72 · see citing works
Polymorphisms of the apolipoprotein and angiotensin converting enzyme genes in young North Karelian patients with coronary heart disease
Miettinen, H. E., Korpela, K., H�m�l�inen, L., & KONTULA, K. K. (1994) · Human Genetics · doi:10.1007/bf00202868 · Cited by 68 · see citing works
Self-citation
Apolipoprotein E-∈A allele and Alzheimer's disease
Anwar, N. M., Lovestone, S., Cheetham, M. E., Levy, R., Powell, J. F., Amouyel, P., Brousseau, T., Fruchart, J., Dallongeville, J., Lucotte, G., et al. (1993) · The Lancet · doi:10.1016/0140-6736(93)92404-h · Cited by 66 · see citing works
Linkage of late-onset Alzheimer's disease with apolipoprotein E type 4 on chromosome 19
Borgaonkar, D., Schmidt, L., Martin, S. E., Kanzer, M. D., Edelsohn, L., Growdon, J. H., & Farrer, L. A. (1993) · The Lancet · doi:10.1016/0140-6736(93)91458-x · Cited by 65 · see citing works
Confirmation that familial clustering and age of onset in late onset Alzheimer's disease are determined at the apolipoprotein E locus
Houlden, H., Crook, R., Hardy, J., Roques, P., Collinge, J., & Rossor, M. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90026-4 · Cited by 38 · see citing works
Alzheimer's disease, apolipoprotein E4, and gender
Payami, H. (1994) · JAMA · doi:10.1001/jama.271.17.1316 · Cited by 19 · see citing works
Staining Senile Plaques using Bodian's Method Modified with Methenamine
Kondoh, H., Matsushita, M., Kosaka, K., & MIYAZAKI, N. (1993) · Biotechnic & Histochemistry · doi:10.3109/10520299309104677 · Cited by 16 · see citing works

Flagged first, then by citations

Sorted by citations

Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063 · see citing works
Alzheimer's Disease Is a Synaptic Failure
Selkoe, D. J. (2002) · Science · doi:10.1126/science.1074069 · Cited by 4,420 · see citing works
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
The Amyloid-β Pathway in Alzheimer’s Disease
Hampel, H., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S. H., Villemagne, V. L., Aisen, P., Vendruscolo, M., Iwatsubo, T., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01249-0 · Cited by 1,952 · 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 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 · see citing works
Exercise Is Associated with Reduced Risk for Incident Dementia among Persons 65 Years of Age and Older
Larson, E. B., Wang, L., Bowen, J. D., McCormick, W. C., Teri, L., Crane, P., & Kukull, W. (2006) · Annals of Internal Medicine · doi:10.7326/0003-4819-144-2-200601170-00004 · Cited by 1,463 · see citing works
Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E
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 · see citing works
Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales
(2001) · The Lancet · doi:10.1016/s0140-6736(00)03589-3 · Cited by 1,338 · see citing works
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 · see citing works
APOE predicts amyloid‐beta but not tau Alzheimer pathology in cognitively normal aging
Morris, J. C., Roe, C. M., Xiong, C., Fagan, A. M., Goate, A. M., Holtzman, D. M., & Mintun, M. A. (2010) · Annals of Neurology · doi:10.1002/ana.21843 · Cited by 830 · 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
ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies
Raulin, A.-C., Doss, S. V., Trottier, Z. A., Ikezu, T. C., Bu, G., & Liu, C.-C. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00574-4 · Cited by 756 · see citing works
Clinicopathologic Studies in Cognitively Healthy Aging and Alzheimer Disease: Relation of Histologic Markers to Dementia Severity, Age, Sex, and Apolipoprotein E Genotype
Berg, 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 · see citing works
ApoE and Aβ in Alzheimer’s Disease: Accidental Encounters or Partners?
Kanekiyo, T., Xu, H., & Bu, G. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.045 · Cited by 608 · see citing works
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 · see citing works
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 · see citing works
Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer’s disease
Chatterjee, P., Pedrini, S., Stoops, E., Goozee, K., Villemagne, V. L., Asih, P. R., Verberk, I. M. W., Dave, P., Taddei, K., Sohrabi, H. R., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-020-01137-1 · Cited by 439 · see citing works
Amyloid β-Peptide Is Transported on Lipoproteins and Albumin in Human Plasma
Biere, A. L., Ostaszewski, B., Stimson, E. R., Hyman, B. T., Maggio, J. E., & Selkoe, D. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.51.32916 · Cited by 331 · see citing works
Genes associated with Alzheimer&#39;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 · see citing works
Apolipoprotein E ε4 allele, AD pathology, and the clinical expression of Alzheimer’s disease
Bennett, D. A., Wilson, R. S., Schneider, J. A., Evans, D. A., Aggarwal, N. T., Arnold, S. E., Cochran, E. J., Berry-Kravis, E., & Bienias, J. L. (2003) · Neurology · doi:10.1212/01.wnl.0000042478.08543.f7 · Cited by 282 · 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
Effect ofAPOEgenotype on amyloid plaque load and gray matter volume in Alzheimer disease
Drzezga, A., Grimmer, T., Henriksen, G., Mühlau, M., Perneczky, R., Miederer, I., Praus, C., Sorg, C., Wohlschläger, A., Riemenschneider, M., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181a2e8d0 · Cited by 248 · see citing works
Differential Relationships of Reactive Astrocytes and Microglia to Fibrillar Amyloid Deposits in Alzheimer Disease
Serrano-Pozo, A., Muzikansky, A., Gómez-Isla, T., Growdon, J. H., Betensky, R. A., Frosch, M. P., & Hyman, B. T. (2013) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3182933788 · Cited by 226 · see citing works
Gangliosides: glycosphingolipids essential for normal neural development and function
Schengrund, C.-L. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.03.007 · Cited by 211 · see citing works
Prevalence of Alzheimer’s disease in very elderly people: A prospective neuropathological study
Polvikoski, T., Sulkava, R., Myllykangas, L., Notkola, I.-L., Niinistö, L., Verkkoniemi, A., Kainulainen, K., Kontula, K., Pérez–Tur, J., Hardy, J., et al. (2001) · Neurology · doi:10.1212/wnl.56.12.1690 · Cited by 197 · see citing works
Self-citation
<scp> APOE </scp> ε2 is associated with milder clinical and pathological <scp>A</scp> lzheimer disease
Serrano‐Pozo, A., Qian, J., Monsell, S. E., Betensky, R. A., & Hyman, B. T. (2015) · Annals of Neurology · doi:10.1002/ana.24369 · Cited by 176 · see citing works
APOE ε2 is associated with intact cognition but increased Alzheimer pathology in the oldest old
Berlau, D. J., Corrada, M. M., Head, E., & Kawas, C. H. (2009) · Neurology · doi:10.1212/01.wnl.0000343853.00346.a4 · Cited by 185 · see citing works
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
Isoform‐Specific Effects of Apolipoproteins E2, E3, and E4 on Cerebral Capillary Sequestration and Blood‐Brain Barrier Transport of Circulating Alzheimer's Amyloid β
Martel, C. L., Mackic, J. B., Matsubara, E., Governale, S., Miguel, C., Miao, W., McComb, J. G., Frangione, B., Ghiso, J., & Zlokovic, B. V. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69051995.x · Cited by 149 · see citing works
Gender and age modify the association between APOE and AD-related neuropathology
Ghebremedhin, E., Schultz, C., Thal, D. R., Rüb, U., Ohm, T. G., Braak, E., & Braak, H. (2001) · Neurology · doi:10.1212/wnl.56.12.1696 · Cited by 108 · see citing works
The Proteasome and Oxidative Stress in Alzheimer's Disease
Bonet-Costa, V., Pomatto, L. C.-D., & Davies, K. J. A. (2016) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6802 · Cited by 99 · 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
Apolipoprotein E and Alzheimer's disease: the protective effects of ApoE2 and E3
Rebeck, G. W., Kindy, M., & LaDu, M. J. (2002) · Journal of Alzheimer's Disease · doi:10.3233/jad-2002-4304 · Cited by 89 · see citing works
Frontal lobe white matter hyperintensities and neurofibrillary pathology in the oldest old
Polvikoski, T. M., van Straaten, E. C. W., Barkhof, F., Sulkava, R., Aronen, H. J., Niinistö, L., Oinas, M., Scheltens, P., Erkinjuntti, T., & Kalaria, R. N. (2010) · Neurology · doi:10.1212/wnl.0b013e318200d6f9 · Cited by 88 · see citing works
Self-citation
The age gap between patients in clinical studies and in the general population: a pitfall for dementia research
Schoenmaker, N., & Van Gool, W. A. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00884-1 · Cited by 86 · see citing works
ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-β1–42
Trommer, B. L., Shah, C., Yun, S. H., Gamkrelidze, G., Pasternak, E. S., Blaine Stine, W., Manelli, A., Sullivan, P., Pasternak, J. F., & LaDu, M. J. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.08.011 · Cited by 82 · see citing works
ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease
Li, Y., Macyczko, J. R., Liu, C.-C., & Bu, G. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.03.011 · Cited by 61 · see citing works
Apolipoprotein E ε4 and Age at Onset of Sporadic and Familial Alzheimer Disease in Caribbean Hispanics
Olarte, L., Schupf, N., Lee, J. H., Tang, M.-X., Santana, V., Williamson, J., Maramreddy, P., Tycko, B., & Mayeux, R. (2006) · Archives of Neurology · doi:10.1001/archneur.63.11.1586 · Cited by 42 · see citing works
Microglia‐specific <scp>ApoE</scp> knock‐out does not alter Alzheimer's disease plaque pathogenesis or gene expression
Henningfield, C. M., Arreola, M. A., Soni, N., Spangenberg, E. E., & Green, K. N. (2022) · Glia · doi:10.1002/glia.24105 · Cited by 40 · see citing works
APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia
Preman, P., Moechars, D., Fertan, E., Wolfs, L., Serneels, L., Shah, D., Lamote, J., Poovathingal, S., Snellinx, A., Mancuso, R., et al. (2024) · EMBO Molecular Medicine · doi:10.1038/s44321-024-00162-7 · Cited by 32 · 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

APOE ε3/ε4 and APOE ε4/ε4 genotypes drive unique gene signatures in the cortex of young micePreprint
Foley, K. E., Garceau, D. T., Kotredes, K. P., Carter, G. W., Sasner, M., & Howell, G. R. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.10.28.359422 · Cited by 3 · see citing works
O4–01–08: Apolipoprotein E inhibits generation of neurotoxic cross–linked beta–amyloid species (CAPS)
Moir, R. D., Chadwick, O., & Tanzi, R. E. (2006) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2006.05.298 · Cited by 1 · see citing works
Relative Abundance of Alzheimer A Beta Amyloid Peptide Variants in Alzheimer Disease and normal Aging
Näslund, J., Schierhorn, A., Hellman, U., Lannfelt, L., Roses, A. D., Tjernberg, L. O., Silberring, J., Gandy, S. E., Winblad, B., & Greengard, P. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.18.8378 · Cited by 468 · see citing works
Amyloid-β Signal Transduction Antagonist, A Possible Way to Relief Alzheimer’s Disease
He, Z. (2023) · Theoretical and Natural Science · doi:10.54254/2753-8818/4/20220567
S4–01–01: Seeded initiation and spread of aggregated beta‐amyloid
Walker, L. C. (2013) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.04.316

Authors: Polvikoski, T., Sulkava, R., Haltia, M., Kainulainen, K., Vuorio, A., Verkkoniemi, A., Niinistö, L., Halonen, P., & Kontula, K.
Affiliations: University of Helsinki (FI)
University of Eastern Finland (FI)
ORCID: Vuorio, Alpo
Kontula, Kimmo
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 1995-11-09
Volume: 333
Issue: 19
Pages: 1242-1248
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejm199511093331902
OpenAlex: W2341558723
Cited by: 493
References: 41
Citations by year: 2026: 5 · 2025: 9 · 2024: 7 · 2023: 15 · 2022: 22 · 2021: 17 · 2020: 19 · 2019: 16 · 2018: 14 · 2017: 10 · 2016: 12 · 2015: 16 · 2014: 10 · 2013: 17 · 2012: 12
FWCI: 21.48
Type: journal article
Language: en
Open access: closed
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: apolipoprotein E, APOE ε4, Alzheimer's disease, dementia, cerebral cortex, neurofibrillary tangles, genetic risk factors, older adults, methenamine silver staining, neuropathology
MeSH terms: Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Apolipoproteins E, Cerebral Cortex, Dementia, DNA, Female, Gene Frequency, Genotype, Humans, Male, Prospective Studies, Cohort Studies, Amyloid beta-Peptides, Neurofibrillary Tangles, 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 E, Dementia, and Cortical Deposition of β-Amyloid Protein

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks