Dissociation of neuropathologic findings and cognition: case report of an apolipoprotein E epsilon2/epsilon2 genotype

Arch Neurol. 2007 Aug;64(8):1193-6. doi: 10.1001/archneur.64.8.1193.


Background: The apolipoprotein E (APOE) epsilon2 allele has been suggested as having a protective effect and delaying the age at onset of Alzheimer disease.

Objective: To describe a dissociation between neuropathologic findings with normal cognition in a woman with severe Alzheimer disease with the APOE epsilon2/epsilon2 genotype.

Design: Case report from a community-based prospective study of persons 90 years or older (The 90+ Study).

Participant: A 92-year-old woman without dementia with the APOE epsilon2/epsilon2 genotype who lived independently without significant cognitive or functional loss and was a participant in The 90+ Study. She died in December 2004, and postmortem examination of her brain was performed.

Intervention: Neurologic examination and a battery of neuropsychological tests were performed 6 months and 1 month before death. Neuropathologic examination included Braak and Braak staging for senile plaques and neurofibrillary tangles.

Results: Neuropathologic examination of the brain revealed advanced senile plaque and neurofibrillary tangle disease consistent with a high likelihood of Alzheimer disease. At clinical evaluation, the participant demonstrated no dementia and only mild cognitive deficits.

Conclusions: The APOE genotype may have contributed to maintenance of cognition despite advanced neuropathologic findings of Alzheimer disease. This case suggests that the APOE epsilon2 isoform may have a protective effect against cognitive decline in Alzheimer disease that may be independent from senile plaques and neurofibrillary tangles.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged, 80 and over
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology*
  • Apolipoprotein E2 / genetics*
  • Brain / pathology*
  • Cognition*
  • Female
  • Genotype
  • Humans
  • Neurofibrillary Tangles / pathology
  • Neurologic Examination
  • Neuropsychological Tests
  • Plaque, Amyloid / pathology


  • Apolipoprotein E2