Apolipoprotein E epsilon4 allele decreases functional connectivity in Alzheimer's disease as measured by EEG coherence

Abstract

Objectives: The epsilon4 allele of apolipoprotein E (APOE) represents a major biological risk factor for late onset Alzheimer's disease. However, it is still not known whether the APOE genotype affects the progression of the disease, assessed by different functional methods.

Methods: The study sample included 41 patients with probable Alzheimer's disease. Subjects had similar severity of disease, age of onset, and duration of illness, and were subcategorised according to their APOE genotypes: 17 with no epsilon4 allele, 14 with one epsilon4 allele, and 10 with two epsilon4 alleles. The control group consisted of 18 healthy subjects comparable with the patients in age and education. Analysed quantitative EEG (qEEG) variables were the ratio of alpha and theta absolute power and EEG coherence in alpha frequency band, representing major cortical association pathways.

Results: There was pronounced EEG slowing in all three patient subgroups compared with the controls for the alpha/theta ratio, but there was no significant difference across the patient subgroups. Patients homozygous for the APOE epsilon4 allele had reduced right and left temporoparietal, right temporofrontal, and left occipitoparietal coherence. Patients without and with one epsilon4 allele showed an overlap between the control group and group with two epsilon4 alleles in coherence measures.

Conclusions: APOE epsilon4 does not influence EEG slowing, an index which reflects severity of the disease in patients with Alzheimer's disease, but seems to be associated with selective decreases in functional connectivity as assessed by EEG coherence. This finding might be of clinical importance when considering different pathogenetic mechanisms.