title: Apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begins in middle age.
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 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.
authors: Department of Forensic Medicine, Medical School, University of Tampere, Tampere, Finland. eloise.kok@uta.fi
authors: Eloise
authors: E
authors: Kok
authors: Satu
authors: S
authors: Haikonen
authors: Teemu
authors: T
authors: Luoto
authors: Heini
authors: H
authors: Huhtala
authors: Sirkka
authors: S
authors: Goebeler
authors: Hannu
authors: H
authors: Haapasalo
authors: Pekka J
authors: PJ
authors: Karhunen
mesh_terms: 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
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; C068937:apolipoprotein E4 (Philadelphia)