SPECT and MRI analysis in Alzheimer's disease: Relation to apolipoprotein E ε4 allele

Abstract

Objectives - The ε4 allele of apolipoprotein E (ApoE) is a risk factor for late onset Alzheimer's disease. ApoE is present in senile plaques, neurofibrillary tangles, and cerebrovascular amyloid, and it is implicated in synaptogenesis. The effect of ApoE polymorphism on the volumes of hippocampus, amygdala, and frontal lobe was studied. The hypothesis was that the patients with Alzheimer's disease carrying the ε4 allele have more pronounced atrophy. The relation of ApoE and cerebral blood flow on cortical areas was also assessed. Methods - Fifty eight patients with Alzheimer's disease at the early stage of the disease and 34 control subjects were studied. Patients with Alzheimer's disease were divided into subgroups according to the number of the ε4 alleles. Volumes were measured by MRI and regional cerebral blood flow ratios referred to the cerebellum were examined by 99mTc-HMPAO SPECT. ApoE genotypes were determined by digestion of ApoE polymerase chain reaction products with the restriction enzyme Hha1. Results - patients with Alzheimer's disease had smaller volumes of hippocampi and amygdala compared with control subjects, and the patients with Alzheimer's disease homozygous for the ε4 allele had the most prominent volume loss in the medial temporal lobe structures. The frontal lobe volumes did not differ significantly. All patients with Alzheimer's disease had bilateral temporoparietal hypoperfusion and the subgroups with one or no ε4 alleles also had frontal hypoperfusion compared with control subjects. The occipital perfusion ratios tended to decrease with increasing number of ε4 alleles. Conclusions - Patients with Alzheimer's disease homozygous for the ε4 allele seem to have severe damage in the medial temporal lobe structures early in the disease process and differ from the patients with Alzheimer's disease with one or no ε4 alleles.