Risk Variants in Three Alzheimer's Disease Genes Show Association with EEG Endophenotypes

Area of Science:

• Neuroscience
• Genetics
• Biomarkers

Background:

• Alzheimer's disease (AD) is a complex neurodegenerative disorder with unexplained heritability.
• Slowing of brain oscillatory activity, measured by electroencephalography (EEG) relative power (RP), is a common physiological alteration in AD.
• RP in conventional frequency bands can serve as endophenotypes for AD.

Purpose of the Study:

• To investigate the association between 16 genes previously linked to AD and the slowing of brain activity.
• To analyze the relationship between genetic variants and electroencephalography (EEG) relative power (RP) in different Alzheimer's disease (AD) stages.

Main Methods:

• An Iberian cohort comprising 45 elderly controls, 45 individuals with mild cognitive impairment, and 109 AD patients was studied.
• Genomic information and brain activity (EEG RP) were analyzed for all participants.
• Association analysis was performed between specific gene variants and RP across frequency bands.

Main Results:

• Slowing of brain activity was observed in carriers of risk alleles in IL1RAP, UNC5C, and NAV2 genes.
• These associations were consistent regardless of AD disease status.
• The observed slowing was independent of major risk factors like age, sex, and APOE ɛ4 presence.

Conclusions:

• Novel genetic associations with AD endophenotypes (slowing of brain activity) were identified.
• Variants in IL1RAP, UNC5C, and NAV2 may play a significant role in AD pathogenesis.
• These findings contribute to understanding AD's complex biological mechanisms and brain physiology.