Relationship between the Presence of the ApoE ε4 Allele and EEG Complexity along the Alzheimer’s Disease Continuum

Abstract

Alzheimer’s disease (AD) is the most prevalent cause of dementia, being considered a major health problem, especially in developed countries. Late-onset AD is the most common form of the disease, with symptoms appearing after 65 years old. Genetic determinants of AD risk are vastly unknown, though, $\epsilon$ 4 allele of the ApoE gene has been reported as the strongest genetic risk factor for AD. The objective of this study was to analyze the relationship between brain complexity and the presence of ApoE $\epsilon$ 4 alleles along the AD continuum. For this purpose, resting-state electroencephalography (EEG) activity was analyzed by computing Lempel-Ziv complexity (LZC) from 46 healthy control subjects, 49 mild cognitive impairment subjects, 45 mild AD patients, 44 moderate AD patients and 33 severe AD patients, subdivided by ApoE status. Subjects with one or more ApoE $\epsilon$ 4 alleles were included in the carriers subgroups, whereas the ApoE $\epsilon$ 4 non-carriers subgroups were formed by subjects without any $\epsilon$ 4 allele. Our results showed that AD continuum is characterized by a progressive complexity loss. No differences were observed between AD ApoE $\epsilon$ 4 carriers and non-carriers. However, brain activity from healthy subjects with ApoE $\epsilon$ 4 allele (carriers subgroup) is more complex than from non-carriers, mainly in left temporal, frontal and posterior regions (p-values < 0.05, FDR-corrected Mann–Whitney U-test). These results suggest that the presence of ApoE $\epsilon$ 4 allele could modify the EEG complexity patterns in different brain regions, as the temporal lobes. These alterations might be related to anatomical changes associated to neurodegeneration, increasing the risk of suffering dementia due to AD before its clinical onset. This interesting finding might help to advance in the development of new tools for early AD diagnosis.