Longer TOMM40 poly‐T variants associated with decreased regional gray matter in cognitively normal older APOE E3/E3 adults: Neuroimaging / imaging and genetics. (7th December 2020)

• Record Type: Journal Article
• Authors: Honea, Robyn A; Vidoni, Eric D; Morris, Jill K; Michaelis, Elias K; Burns, Jeffrey M; Swerdlow, Russell H
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.040645
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: The TOMM40 poly‐T is a polymorphism of the TOMM40 gene at rs10524523 ("523"), in linkage disequilibrium with APOE. The role of TOMM40 in Alzheimer's disease risk is still controversial. We sought to use whole brain voxel‐based methods to investigate if older individuals with the absence of an APOE e4 allele with varying lengths of the TOMM40 Poly‐T allele had gray matter volume differences indicative of Alzheimer's disease risk. Method: We studied individuals without cognitive impairment (n=69) from our KU Alzheimer's Disease Center whose apolipoprotein (APOE) genotype was e3/e3, and who were Caucasian. The participants were grouped according to poly‐T length polymorphisms at "523" homozygous for S (S/S; n=25), homozygous for VL (VL/VL; n=19), and heterozygous (S/VL; n=25). All individuals were scanned for T1‐weighted MPRAGE structural images using a 3T Skyra Siemens. Images were preprocessed and analyzed using CAT12, a Computational Anatomy Toolbox (http://www.neuro.uni‐jena.de/cat/) running under SPM12 and MATLAB (R2020a). To investigate associations between genotype and regional GM volume, we performed voxel‐based morphometry (VBM). In order to investigate associations between TOMM40 Poly‐T group and gray matter volume differences we included age, sex, and total intracranial volume (TIV), as variables of no interest in our full factorial model. The statistical threshold was set at Pheight < 0.05, corrected (FDR). Result: All groups were similar and not significantly different in mean age, education, MMSE, and overall brain volume. Brain magnetic resonance scans were analyzed using the CAT12 program within SPM software. Individuals with a VL/VL genotype had lower precuneus volumes (p=.023 FDR corrected, k=213, ‐29, ‐84, 36) and temporal cortex volumes (p=.005 FDR corrected, k =362, ‐45, ‐40, ‐32) compared to S/S individuals. Conclusion: TOMM40 "523" VL variants are related to reduced gray matter volume in the precuneus and temporal cortex in healthy individuals with an APOE e3/e3genotype. This is especially interesting as the precuneus has been identified in other studies, and it may be particularly sensitive to dysfunction in bioenergetic changes associated with faulty mitochondria. This adds to a growing literature implicating TOMM40 "523" and mitochondrial function in late‐onset Alzheimer's disease progression.