VOLUMES OF HIPPOCAMPUS, AMYGDALA AND FRONTAL-LOBE IN ALZHEIMER PATIENTS WITH DIFFERENT APOLIPOPROTEIN-E GENOTYPES

An increased frequency of apolipoprotein E E4 allele has been reported in patients with late onset Alzheimer's disease. Apolipoprotein E participates in the transport of cholesterol and other lipids and interferes with the growth and regeneration of both peripheral and central nervous system tissues during development and after injury. Apolipoprotein E is also implicated in synaptogenesis. Apolipoprotein E isoforms differ in binding to amyloid-beta-protein and tau protein in vitro. Here, we wanted to study the effect of apolipoprotein E genotype on the magnitude of damage in the hippocampus, where a marked synapse loss exists in Alzheimer's disease. We measured by magnetic resonance imaging the volumes of the hippocampus, amygdala, and frontal lobes in the three Alzheimer subgroups: patients with 2, 1 or 0 E4 alleles. We also investigated the profile of deficits on tests assessing memory, language, visuospatial, executive, and praxic functions of these Alzheimer subgroups. All Alzheimer patients were at early stage of the disease. We found that Alzheimer patients with E4/4 genotype (N = 5) had smaller volumes of the hippocampus and the amygdala than those with E3/4 (N = 9) and those with E3/3 or E2/3 (N = 12). The difference was significant for the right hippocampus (-54% of control) and the right amygdala (-37% of control). The volumes of the frontal lobes were similar across the Alzheimer subgroups. The patients with E4/4 also showed lowest scores on delayed memory tests and differed from E3/3, 3/2 patients in the list learning test (<0.05). The Alzheimer subgroups did not differ in age, age at onset, the global clinical severity of dementia or in the profile of other neuropsychological deficits. The results suggest that Alzheimer patients with apolipoprotein E E4/4 genotype have severe damage of the hippocampus and amygdala very early in the disease process and differ from Alzheimer patients with one or no E4 allele. Whether this larger volume loss in the hippocampus is related to increased accumulation of the amyloid and paired helical filaments or greater loss of synapses in E4 homozygous Alzheimer patients, is of interest and worth studying.