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 par ticipates in the transport of cholesterol and other lipids and interfe res with the growth and regeneration of both peripheral and central ne rvous system tissues during development and after injury. Apolipoprote in E is also implicated in synaptogenesis. Apolipoprotein E isoforms d iffer in binding to amyloid-beta-protein and tau protein in vitro. Her e, we wanted to study the effect of apolipoprotein E genotype on the m agnitude of damage in the hippocampus, where a marked synapse loss exi sts in Alzheimer's disease. We measured by magnetic resonance imaging the volumes of the hippocampus, amygdala, and frontal lobes in the thr ee Alzheimer subgroups: patients with 2, 1 or 0 E4 alleles. We also in vestigated the profile of deficits on tests assessing memory, language , visuospatial, executive, and praxic functions of these Alzheimer sub groups. All Alzheimer patients were at early stage of the disease. We found that Alzheimer patients with E4/4 genotype (N = 5) had smaller v olumes 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 sco res on delayed memory tests and differed from E3/3, 3/2 patients in th e list learning test (<0.05). The Alzheimer subgroups did not differ i n age, age at onset, the global clinical severity of dementia or in th e profile of other neuropsychological deficits. The results suggest th at Alzheimer patients with apolipoprotein E E4/4 genotype have severe damage of the hippocampus and amygdala very early in the disease proce ss and differ from Alzheimer patients with one or no E4 allele. Whethe r this larger volume loss in the hippocampus is related to increased a ccumulation of the amyloid and paired helical filaments or greater los s of synapses in E4 homozygous Alzheimer patients, is of interest and worth studying.