Gene dose of the ε4 allele of apolipoprotein E and disease progression in sporadic late‐onset alzheimer's disease
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A strong association has been described in cross‐sectional studies between the ε4 allele of the apolipoprotein E and late‐onset Alzheimer's disease (LOAD). This study addresses the relationship between disease progression and the ε4 allele in 62 sporadic LOAD (onset at age 70 and over) patients. Disease progression was estimated retrospectively with the Mini‐Mental State Examination (MMSE) amounting to 4.7, 3.8, and 2.2 points per year (sex‐adjusted test for trend: p = 0.01) and with the Clinical Dementia Rating (CDR) to 0.76, 0.67, and 0.42 units per year (p = 0.03) in ‐/‐, ε4/‐, and ε4/ε4 patients. The proportion of patients with fast progression decreased (p ≤ 0.005) and with slow progression increased (p = 0.002) with increasing ε4 gene dose. These findings were confirmed in a smaller sample of 28 patients for whom longitudinal assessments of MMSE were available and when nonlinear progression of the disease was accounted for in a stratified analysis. These data suggest that disease duration might be longer in ε4 carriers and that this might at least partly account for the cross‐sectional association between the ε4 allele and LOAD.
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There have been numerous conflicting reports regarding whether different apoE alleles influence the rate of cognitive decline following dementia onset.
“While the effect of the ε4 allele on the risk and age of onset for AD is generally consistent in most studies, there have been numerous conflicting reports regarding whether different apoE alleles influence the rate of cognitive decline following dementia onset (Asada et al., 1996; Craft et al., 1998; Frisoni et al., 1995; Growdon et al., 1996; Hoyt et al., 2005; Kurz et al., 1996).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Frisoni et al., 1995
Cites
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
Genetic associations with human longevity at the APOE and ACE loci
Schächter, F., Faure-Delanef, L., Guénot, F., Rouger, H., Froguel, P., Lesueur-Ginot, L., & Cohen, D. (1994) · Nature Genetics · doi:10.1038/ng0194-29 · Cited by 1,095 · see citing works
The Natural History of Alzheimer's Disease: Description of Study Cohort and Accuracy of Diagnosis
Becker, J. T. (1994) · Archives of Neurology · doi:10.1001/archneur.1994.00540180063015 · Cited by 576 · 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
PREVALENCE, INCIDENCE AND DURATION
FREEMAN, J., & HUTCHISON, G. B. (1980) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a113043 · Cited by 224 · 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
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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
Gold, M., Alderton, C., Zvartau-Hind, M., Egginton, S., Saunders, A. M., Irizarry, M., Craft, S., Landreth, G., Linnamägi, Ü., & Sawchak, S. (2010) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000318845 · Cited by 361 · see citing works
APOE ε4 allele predicts faster cognitive decline in mild Alzheimer disease
Cosentino, S., Scarmeas, N., Helzner, E., Glymour, M. M., Brandt, J., Albert, M., Blacker, D., & Stern, Y. (2008) · Neurology · doi:10.1212/01.wnl.0000304038.37421.cc · Cited by 214 · see citing works
LANGE, K. L., BONDI, M. W., SALMON, D. P., GALASKO, D., DELIS, D. C., THOMAS, R. G., & THAL, L. J. (2002) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617702870096 · Cited by 129 · 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
APOE and other loci affect age‐at‐onset in Alzheimer's disease families with PS2 mutation
Wijsman, E. M., Daw, E. W., Yu, X., Steinbart, E. J., Nochlin, D., Bird, T. D., & Schellenberg, G. D. (2005) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30087 · Cited by 79 · see citing works
Ma, C., Wang, J., Zhang, J., Chen, K., Li, X., Shu, N., Chen, Y., Liu, Z., & Zhang, Z. (2017) · Molecular Neurobiology · doi:10.1007/s12035-016-0224-5 · Cited by 21 · see citing works
- Authors
- Frisoni, G. B., Govoni, S., Geroldi, C., Bianchetti, A., Calabresi, L., Franceschini, G., & Trabucchi, M.
- Affiliations
- Gruppo di Ricerca Geriatrica (IT)
- University of Milan (IT)
- Corresponding author
- Frisoni, Giovanni B.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 1995-05
- Volume
- 37
- Issue
- 5
- Pages
- 596-604
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2041394188
- Cited by
- 149
- References
- 6
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 4 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 7.72
- Type
- journal article
- Language
- en
- Open access
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- apolipoprotein E, APOE ε4, gene dosage, late-onset Alzheimer's disease, disease progression, genetic association, Mini-Mental State Examination, Clinical Dementia Rating, disease duration
- MeSH terms
- Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Analysis of Variance, Apolipoproteins E, Female, Humans, Male, Phenotype, Age of Onset, Disease Progression, Gene Dosage
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