Apolipoprotein E ε4 allele and whole brain atrophy in late-onset Alzheimer's disease

Objective: Diffuse brain atrophy is one of the gross pathological features of Alzheimer's disease and is a result of degenerative changes. The ε4 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 ε4 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 ε4 alleles (N=62), one ε4 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 ε4 alleles; i.e., patients carrying two APOE ε4 alleles had the least brain atrophy. This association between the APOE ε4 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 progresses before severe brain atrophy develops in patients carrying the APOE ε4 allele and suggest that an APOE ε4-allele-related mechanism that affects neuronal function before a decrement in brain matter is involved in the development of dementia.