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The apolipoprotein E (APOE) ε4 allele is a risk factor for Alzheimer's disease (AD), but its effect on brain volumes is controversial. We explored the effect of the ε4 allele on regional cortical thickness and volume measurements using an automated pipeline in 111 subjects with mild cognitive impairment (MCI), 115 AD patients, and 107 age-matched healthy controls. The clinical data were used as covariates in the thickness and volume comparisons. The ε4 carriers had significantly smaller volume than non-carriers in caudate (p=0.028) in controls; in amygdala and caudate in the MCI group (p <or= 0.049); and in hippocampus and amygdala in the AD group (p <or= 0.001). In the female subjects, the ε4 carriers had significantly thinner cortical thickness or smaller volume than non-carriers in medial orbitofrontal gyrus and caudate in controls (p <or= 0.014); in amygdala in MCI subjects (p=0.047) and in hippocampus and amygdala in AD patients (p <or= 0.024). However, in the male subjects, there were significant differences in cortical thickness and volume between ε4 carriers and non-carriers in several structures in the MCI group, but no differences in the controls and AD patients. Compared to the non-carriers, the homozygous ε4 carriers showed significant volume loss in hippocampus, deep nuclei, and caudal anterior cingulate cortex in MCI. In the AD group, the homozygous ε4 carriers had significant volume loss in hippocampus and amygdala. We conclude that the APOE ε4 allele modulates regional cortical thickness and volume in relation to diagnostic group and gender. The ε4 allele has a dose-dependent and regionally specific effect on brain structures.

Original publication




Journal article


J Alzheimers Dis

Publication Date





947 - 966


Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Amygdala, Apolipoprotein E4, Cerebral Cortex, Cognition Disorders, Female, Gene Frequency, Genotype, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Risk Factors, Sex Factors