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PubMed · 42508146

Subtle cortical thinning in the temporal pole in middle-aged APOE-ε4 and PICALM (rs3851179) AA/AG carriers without dementia.

Patrycja Dzianok·Jakub Wojciechowski·Tomasz Wolak·Ewa Kublik
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Abstract

The symptoms of Alzheimer's disease (AD) are caused by neurodegeneration and atrophy in particular brain regions, especially in the temporal lobe. However, the influence of genetic risk on cortical thickness prior to dementia onset, remains unclear. This study aimed to explore the relationship between AD genetic risk (related to APOE and PICALM genes) and cortical thickness in selected regions of interest (ROIs) in middle-aged individuals without dementia. Sixty-nine (N = 69) participants (34 females, 35 males; age: 55.45 ± 3.19) underwent magnetic resonance imaging (MRI). They were divided into three groups based on their genetic AD risk: A+ P+ (APOE/PICALM risk variants), A+P- (APOE risk variant, PICALM neutral variants), and the N group (APOE/PICALM neutral alleles). Cortical thickness was analyzed using CAT12 software (surface-based morphometry with the Destrieux atlas) based on T1-weighted MR images in five ROIs referred to as "the cortical signature of AD" in previous studies. The A+P- group had a thinner right temporal pole cortex than non-carriers after controlling for sex, age, and Raven's Progressive Matrices scores. Although this finding did not survive FDR correction across the 10 tested regions, it is consistent with our hypotheses and prior literature. No other differences in cortical thickness were found in the analyzed regions of AD "signature". The observed effect was restricted to single-risk APOE carriers without PICALM risk alleles. Therefore, further research is needed to understand the genetic interplay between these two genes in conferring AD risk.

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HumansFemaleMaleApolipoprotein E4Magnetic Resonance ImagingMonomeric Clathrin Assembly ProteinsAlzheimer DiseaseTemporal LobeMiddle AgedHeterozygoteGenetic Association StudiesGenetic Predisposition to DiseaseCerebral Cortical ThinningRiskAllelesAPOEAlzheimer’s diseaseCortical thicknessMRIPICALMJournal Article

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Patrycja Dzianok, Jakub Wojciechowski, Tomasz Wolak, Ewa Kublik. 2026-07-21. Subtle cortical thinning in the temporal pole in middle-aged APOE-ε4 and PICALM (rs3851179) AA/AG carriers without dementia.. https://doi.org/10.1016/j.neurobiolaging.2026.07.004

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Journal Article resourceAlleles subjectAlzheimer Disease subjectAlzheimer’s disease subjectFemale subjectGenetic Predisposition to Disease subjectHumans subjectJournal Article subjectMRI subjectMagnetic Resonance Imaging subjectMale subjectMiddle Aged subject

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