Apolipoprotein E ε4 and the pattern of regional brain atrophy in Alzheimer's disease

Background: Although the APOE ε4 allele increases the risk of developing AD, the effects of the ε4 allele on brain atrophy in clinical AD patients are controversial. Objective: To investigate a possible relationship between the genetic variants of APOE and brain atrophy in patients with AD. Methods: Using MRI-based volumetry techniques, the authors compared the volumes of the hippocampal formation, amygdaloid complex, and whole brain in probable AD patients (based on criteria of the National Institute for Neurological and Communicative Disorders and Stroke/ Alzheimer's Disease and Related Disorders Association) with different APOE alleles. One group (n = 46) had the ε3/3 allele, one group (n = 46) had the ε3/4 allele, and one group (n = 46) had the ε4/4 allele. The three groups were matched for age, sex, disease duration, education level, and severity of dementia represented by their score of the Mini-Mental State Examination. A possible difference in pattern of cognitive deficits with dose of the APOE ε4 allele was also examined. Results: The normalized hippocampal volume was correlated with the number of APOE ε4 alleles (r = - 0.285, p = 0.0007). The amygdalar volume was also correlated with the number of APOE ε4 alleles (r = -0.178, p = 0.037). The number of APOE ε4 alleles was positively correlated with the whole-brain volume (r = 0.185, p = 0.030). It was also correlated with Wechsler Adult Intelligence Scale-Revised performance IQ (r = 0.203, p = 0.017) and with Wechsler Memory Scale-Revised attention/concentration score (r = 0.191, p = 0.025). Conclusions: Different patterns of regional brain atrophy were found among patients of different APOE genotypes. The effect of APOE ε4 allele on the brains of AD patients may have regional specificity.