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Am J Psychiatry 155:779-784, June 1998
© 1998 American Psychiatric Association

Regular Article

Apolipoprotein E {epsilon}4 Allele and Whole Brain Atrophy in Late-Onset Alzheimer's Disease

Minoru Yasuda, M.D., Etsuro Mori, M.D., Hajime Kitagaki, M.D., Hikari Yamashita, M.A., Nobutsugu Hirono, M.D., Kenichi Shimada, M.D., Kiyoshi Maeda, M.D., and Chikako Tanaka, M.D., Ph.D.

OBJECTIVE: Diffuse brain atrophy is one of the gross pathological features of Alzheimer's disease and is a result of degenerative changes. The {epsilon}4 allele of apolipoprotein E (APOE) is a risk factor or susceptibility gene in late-onset sporadic Alzheimer's disease and may influence the pathological changes associated with the disease. The aim of this study was to examine the relationship between the APOE {epsilon}4 allele and whole brain atrophy. METHOD: Whole brain volume was quantified by using high-resolution magnetic resonance imaging and the computerized brain segmentation technique in 178 patients with late-onset sporadic Alzheimer's disease who carried no APOE {epsilon}4 alleles (N=62), one {epsilon}4 allele (N=93), or two (N=23) and had comparable clinical severity of dementia. RESULTS: An apparent positive correlation was found between normalized whole brain volume (relative to total intracranial volume) and number of APOE {epsilon}4 alleles; i.e., patients carrying two APOE {epsilon}4 alleles had the least brain atrophy. This association between the APOE {epsilon}4 allele and brain volume was similar in women and men and was independent of age, level of education, duration of illness since symptom onset, and severity of dementia. CONCLUSIONS: The results indicate that cognitive dysfunction pro~gresses before severe brain atrophy develops in patients carrying the APOE {epsilon}4 allele and suggest that an APOE {epsilon}4-allele-related mechanism that affects neuronal function before a decrement in brain matter is involved in the development of dementia.




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