Open AccessRisk Variants in Three Alzheimer’s Disease Genes Show Association with EEG Endophenotypes
Author(s) -
Ana Macedo,
Carlos Gómez,
Marise Souto Rebelo,
Jesús Poza,
Iva Gomes,
Sandra Martins,
Aarón Maturana-Candelas,
Víctor Gutiérrez-de Pablo,
Luís Durães,
Patrícia Sousa,
Manuel Figueruelo,
M. C. Rodríguez,
Carmen Pita,
Miguel Arenas,
Luis Álvarez,
Roberto Hornero,
Alexandra Lopes,
Nádia Pinto
Publication year - 2021
Publication title -
journal of alzheimer's disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.677
H-Index - 139
eISSN - 1875-8908
pISSN - 1387-2877
DOI - 10.3233/jad-200963
Subject(s) - endophenotype , apolipoprotein e , disease , dementia , electroencephalography , alzheimer's disease , medicine , psychology , neuroscience , bioinformatics , biology , cognition
Background: Dementia due to Alzheimer’s disease (AD) is a complex neurodegenerative disorder, which much of heritability remains unexplained. At the clinical level, one of the most common physiological alterations is the slowing of oscillatory brain activity, measurable by electroencephalography (EEG). Relative power (RP) at the conventional frequency bands (i.e., delta, theta, alpha, beta-1, and beta-2) can be considered as AD endophenotypes. Objective: The aim of this work is to analyze the association between sixteen genes previously related with AD: APOE, PICALM, CLU, BCHE, CETP, CR1, SLC6A3, GRIN2 β, SORL1, TOMM40, GSK3 β, UNC5C, OPRD1, NAV2, HOMER2, and IL1RAP, and the slowing of the brain activity, assessed by means of RP at the aforementioned frequency bands. Methods: An Iberian cohort of 45 elderly controls, 45 individuals with mild cognitive impairment, and 109 AD patients in the three stages of the disease was considered. Genomic information and brain activity of each subject were analyzed. Results: The slowing of brain activity was observed in carriers of risk alleles in IL1RAP (rs10212109, rs9823517, rs4687150), UNC5C (rs17024131), and NAV2 (rs1425227, rs862785) genes, regardless of the disease status and situation towards the strongest risk factors: age, sex, and APOE ɛ4 presence. Conclusion: Endophenotypes reduce the complexity of the general phenotype and genetic variants with a major effect on those specific traits may be then identified. The found associations in this work are novel and may contribute to the comprehension of AD pathogenesis, each with a different biological role, and influencing multiple factors involved in brain physiology.