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

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.