Original Article

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

  1. Eloise Kok BScHons1,2,*,
  2. Satu Haikonen MD1,2,
  3. Teemu Luoto MD1,2,
  4. Heini Huhtala MSc3,
  5. Sirkka Goebeler MD1,2,
  6. Hannu Haapasalo MD, PhD4,
  7. Pekka J. Karhunen MD, PhD1,2

Article first published online: 18 MAR 2009

DOI: 10.1002/ana.21696

Issue

Annals of Neurology

Annals of Neurology

Volume 65, Issue 6, pages 650–657, June 2009

Additional Information

How to Cite

Kok, E., Haikonen, S., Luoto, T., Huhtala, H., Goebeler, S., Haapasalo, H. and Karhunen, P. J. (2009), Apolipoprotein E–dependent accumulation of Alzheimer disease–related lesions begins in middle age. Annals of Neurology, 65: 650–657. doi: 10.1002/ana.21696

Author Information

  1. 1

    Department of Forensic Medicine, Medical School, University of Tampere, Tampere, Finland

  2. 2

    Center for Laboratory Medicine, Tampere University Hospital, Tampere, Finland

  3. 3

    School of Public Health, Medical School, University of Tampere, Tampere, Finland

  4. 4

    Department of Pathology, Center for Laboratory Medicine, Tampere University Hospital, Tampere, Finland

*University of Tampere, Medical School, FIN-33014, Tampere, Finland

  1. †

    Potential conflict of interest: All authors declare that they have no competing interests.

Publication History

  1. Issue published online: 25 JUN 2009
  2. Article first published online: 18 MAR 2009
  3. Accepted manuscript online: 18 MAR 2009 12:00AM EST
  4. Manuscript Accepted: 27 FEB 2009
  5. Manuscript Revised: 3 FEB 2009
  6. Manuscript Received: 15 NOV 2007

Funded by

  • Medical Research Fund of Tampere University Hospital
  • Pirkanmaa Regional Fund of the Finnish Cultural Foundation
  • Finnish Foundation for Cardiovascular Research
  • Yrjö Jahnsson Foundation

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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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