Genetic dissection of Hippocampal sclerosis MRI surrogates

Abstract

AbstractBackgroundHippocampal sclerosis of aging (HS) is one of the most predominant causes of dementia in elder populations and it is often misdiagnosed as Alzheimer’s disease (AD). HS has recently been found to show a hippocampal atrophy pattern that might be key for the differentiation of this pathology from AD in the early stages of dementia.MethodIn this study, we aimed to find SNPs associated with AD diagnosis that might be related to HS. To that end, we calculated a polygenic risk score (PRS) combining SNPs associated with AD by Bellenguez et al. (2022) and assessed their relation with HS‐by‐proxy based on magnetic resonance imaging (MRI) data of hippocampal subfield volumes from 1,130 individuals without dementia syndrome.ResultOur results show a significant association of AD‐PRS with fimbria and hippocampal body and head volumes. Association with these hippocampal subfields was also observed on the individual effects of the AD‐related variants in the SHARPIN (rs34173062) and TNIP1 (rs871269) genes. Besides, these loci remained consistently associated to HS‐aging after increasing the sample size by including an independent cohort of healthy individuals (N = 729).ConclusionThe results presented in this study suggest that some SNPs that have recently been identified as AD variants might be closely related to atrophy in hippocampal subfields instead of AD, and hence, could be instrumental to refine AD and HS pathways, their interrelationships, and to elaborate specific treatment for each condition.