Cited by 299Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Apolipoprotein E–dependent accumulation of Alzheimer disease–related lesions begins in middle age

Kok, Eloise, Haikonen, Satu, Luoto, Teemu, Huhtala, Heini, Goebeler, Sirkka, Haapasalo, Hannu, Karhunen, Pekka J.·2009·Annals of Neurology

DOI 10.1002/ana.21696

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Abstract

Objective: To study the prevalence and age dependency of senile plaques (SP) and neurofibrillary tangles (NFT), the brain changes characteristic of Alzheimer disease (AD), and their association with apolipoprotein E (APOE) genotypes in a community‐dwelling normal population. Methods: This neuropathological study used both silver staining and Aβ immunohistochemistry in brain tissue microarrays, including SP coverage and NFT counts from frontal cortex and hippocampus, and APOE genotyping, and was performed on a consecutive prospective series of 603 subjects (aged between 0 and 97 years) of an unselected population living outside of institutions. Cases were subjected to autopsy following sudden or unexpected out‐of‐hospital death, covering 22.1% of the mortality of Tampere, Finland and its surroundings. None died of AD, although 22 (3.7%) were demented and 10 (1.7%) had memory problems. Results: Of the series, 30.8% had SP, and 42.1% had NFT; these occurred more commonly among females and showed a strong relationship with age. Both changes had already appeared at around 30 years of age, reaching an occurrence of almost 100% in the oldest. SP were more frequent in APOE ϵ4‐carriers compared with noncarriers in every age group except the oldest (>90 years). The difference was most evident during the ages 50 to 59 years, where 40.7% of ϵ4‐carriers had SP, compared with 8.2% in noncarriers (odds ratio, 8.39; 95% confidence interval, 2.55–27.62). The difference in NFT prevalence between APOE genotypes was not statistically significant in any age group. Interpretation: The brain changes associated with AD may already begin developing early in middle age, especially among APOE ϵ4 carriers. Ann Neurol 2009;65:650–657

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Authors: Kok, E., Haikonen, S., Luoto, T., Huhtala, H., Goebeler, S., Haapasalo, H., & Karhunen, P. J.
Affiliations: Tampere University (FI)
Tampere University Hospital (FI)
Corresponding author: Kok, Eloise
Haikonen, Satu
Luoto, Teemu
Huhtala, Heini
Goebeler, Sirkka
Haapasalo, Hannu
Karhunen, Pekka J.
ORCID: Kok, Eloise
Luoto, Teemu
Huhtala, Heini
Goebeler, Sirkka
Haapasalo, Hannu
Karhunen, Pekka J.
Venue: Annals of Neurology
Publisher: Wiley
Published: 2009-06
Volume: 65
Issue: 6
Pages: 650-657
ISSN: 0364-5134 (ISSN-L)
1531-8249
DOI: 10.1002/ana.21696
OpenAlex: W2002776021
Cited by: 299
References: 39
Citations by year: 2026: 12 · 2025: 9 · 2024: 9 · 2023: 17 · 2022: 21 · 2021: 20 · 2020: 16 · 2019: 25 · 2018: 15 · 2017: 13 · 2016: 22 · 2015: 13 · 2014: 21 · 2013: 16 · 2012: 22
FWCI: 15.24
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Annals of Neurology (publishedVersion)
PubMed (publishedVersion)
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 › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: Alzheimer's disease, apolipoprotein E, APOE ε4, amyloid plaques, neurofibrillary tangles, middle age (human life stage), age-related prevalence, frontal cortex, hippocampus, sex differences, community-dwelling population, autopsy
MeSH terms: Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Apolipoproteins E, Child, Child, Preschool, Female, Genetic Carrier Screening, Humans, Infant, Infant, Newborn, Male, Middle Aged, Prospective Studies, Cohort Studies, Apolipoprotein E4, Young Adult, Plaque, Amyloid

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Apolipoprotein E–dependent accumulation of Alzheimer disease–related lesions begins in middle age

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