Apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begins in middle age.
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 A beta 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 epsilon 4-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 epsilon 4-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.


CONCLUSIONS
The brain changes associated with AD may already begin developing early in middle age, especially among APOE epsilon 4 carriers.
Kok
Eloise
E
Department of Forensic Medicine, Medical School, University of Tampere, Tampere, Finland. eloise.kok@uta.fi
Haikonen
Satu
S
Luoto
Teemu
T
Huhtala
Heini
H
Goebeler
Sirkka
S
Haapasalo
Hannu
H
Karhunen
Pekka J
PJ
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics / Q000502:physiology; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology*; D011446:Prospective Studies; D055815:Young Adult
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; C068937:apolipoprotein E4 (Philadelphia)