Influence of PICALM and CLU risk variants on beta EEG activity in Alzheimer\u2019s disease patients

Aarón Maturana-Candelas,Alexandra M Lopes,Jesús Poza,Víctor Rodríguez-González,Nadia Pinto,Roberto Hornero,Carlos Gómez,Vìctor Gutiérrez-De Pablo

doi:10.1038/s41598-021-99589-y

Abstract

PICALM and CLU genes have been linked to alterations in brain biochemical processes that may have an impact on Alzheimer’s disease (AD) development and neurophysiological dynamics. The aim of this study is to analyze the relationship between the electroencephalographic (EEG) activity and the PICALM and CLU alleles described as conferring risk or protective effects on AD patients and healthy controls. For this purpose, EEG activity was acquired from: 18 AD patients and 12 controls carrying risk alleles of both PICALM and CLU genes, and 35 AD patients and 12 controls carrying both protective alleles. Relative power (RP) in the conventional EEG frequency bands (delta, theta, alpha, beta, and gamma) was computed to quantify the brain activity at source level. In addition, spatial entropy (SE) was calculated in each band to characterize the regional distribution of the RP values throughout the brain. Statistically significant differences in global RP and SE at beta band (p-values < 0.05, Mann–Whitney U-test) were found between genotypes in the AD group. Furthermore, RP showed statistically significant differences in 58 cortical regions out of the 68 analyzed in AD. No statistically significant differences were found in the control group at any frequency band. Our results suggest that PICALM and CLU AD-inducing genotypes are involved in physiological processes related to disruption in beta power, which may be associated with physiological disturbances such as alterations in beta-amyloid and neurotransmitter metabolism.

Highlights

Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide, with an estimate of over 50 million affected people in 20191
Relative power (RP) in each regions of interest (ROI) was calculated for 53 AD patients (18 with risk alleles of both PICALM and CLU genes and 35 with the protective variants) and 24 healthy controls (12 with risk alleles and 12 with protective alleles) in the traditional frequency bands
The observed disturbances in each single frequency band are in line with the typical spectral alterations found in dementia[46], which suggests that risk genotypes may be associated with worse cognitive status

Summary

Introduction

Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide, with an estimate of over 50 million affected people in 20191. Ponomareva et al.[33] investigated the EEG from healthy subjects and obtained higher power in alpha-3 band (10.9–12.9 Hz) in the CLU CC allele group, in addition to higher beta power and lower alpha inter-hemispheric connectivity in the PICALM GG allele group[34,35] These insights reveal an association between abnormal power fluctuations and certain SNPs in PICALM and CLU, which could be linked to dysfunctions caused by higher A β accumulations or disrupted neurotransmission mechanisms, even in pre-clinical stages of the d isease[33,34,35]. This study is aimed at analyzing source-level EEG in AD patients and healthy controls with risk and protective alleles of PICALM and CLU in order to detect which alterations of brain electrical dynamics could be potentially connected to localized A β presence and neurotransmission deficits

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