Abstract

AbstractBackgroundThe study of the effects that certain genetic risk factors for Alzheimer’s disease (AD) has become a growing body of research. However, the relationship between brain integrity and performance and genetic profiles has been scarcely investigated. Here, we have calculated a genetic risk score (GRS), associated with an enhanced risk of developing AD. The GRS has been computed as the sum of the manifested risk alleles of 3 genetic polymorphisms for the CLU, PICALM and CR1 genes, each one weighted with the logarithm of its odds ratio. Additionally, we have carried out an eyes‐closed, resting‐state magnetoencephalography (MEG) study and analysed the brain functional connectivity (FC) of 230 cognitively intact elders non carriers of the APOE‐4 allele.Method230 healthy elders (aged from 61 to 85) were recruited from the Hospital Universitario San Carlos and the Center for elders at the Chamartín District, all located in Madrid, Spain. All of them underwent a neuropsychological evaluation, MRI assessment and MEG recordings.ResultBeta band FC showed a selective vulnerability to the increased genetic risk that was captured by the GRS score. A clear pattern of hypersynchronization emerged in those participants with higher GRS scores.ConclusionGRS seems to be modulating electrophysiological brain activity inducing alterations in the beta band FC. To the best of our knowledge, this is the first MEG neuroimaging‐genetic approach within an elderly population that considers the possible association of a GRS for AD on brain neurophysiological activity.

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