APOLIPOPROTEIN-E EPSILON-4 ALLELE AND WHOLE-BRAIN ATROPHY IN LATE-ONSET ALZHEIMERS-DISEASE

Objective: Diffuse brain atrophy Is one of the gross pathological feat ures of Alzheimer's disease and is a result of degenerative changes. T he epsilon 4 allele of apolipoprotein E (APOE) is a risk factor or sus ceptibility gene in late-onset sporadic Alzheimer's disease and may in fluence 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 quan tified by using high-resolution magnetic resonance imaging and the com puterized 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 cl inical severity of dementia. Results: An apparent positive correlation was found between normalized whole brain volume (relative to total in tracranial volume) and number of APOE epsilon 4 alleles; i.e., patient s carrying two APOE epsilon 4 alleles had the least brain atrophy. Thi s association between the APOE epsilon 4 allele and brain volume was s imilar in women and men and was independent of age, level of education , duration of illness since symptom onset, and severity of dementia. C onclusions: The results indicate that cognitive dysfunction progresses before severe brain atrophy develops in patients carrying the APOE ep silon 4 allele and suggest that an APOE epsilon 4-allele-related mecha nism that affects neuronal function before a decrement in brain matter is involved in the development of dementia.