Association of TMEM106B with Cortical APOE Gene Expression in Neurodegenerative Conditions

• Published in: Genes 2024-03, Vol.15 (4), p.416
• Main Authors: Picard, Cynthia, Miron, Justin, Poirier, Judes
• Format: Article
• Language: English
• Subjects: Aged; Aging; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Animals; Apolipoprotein E; Apolipoprotein E4; Apolipoproteins E - genetics; Autophagy; Brain research; Cognitive ability; Consent; Cortex (entorhinal); Dementia; Disease; Disease Models, Animal; E protein; Female; Gene expression; Genetic diversity; Genome-Wide Association Study; Genotype & phenotype; Hippocampus; Hippocampus - metabolism; Homeostasis; Humans; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurodegeneration; Neurodegenerative diseases; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - metabolism; Neurons; Pathology; Proteins; Proteomics; Quality control; Reinnervation; Religious orders; Risk factors; Temporal cortex; Transcriptomics
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes15040416

The e4 allele of the apolipoprotein E gene is the strongest genetic risk factor for sporadic Alzheimer's disease. Nevertheless, how is regulated is still elusive. In a -eQTL analysis, we found a genome-wide significant association between transmembrane protein 106B ( ) genetic variants and cortical mRNA levels in human brains. The goal of this study is to determine whether TMEM106B is mis-regulated in Alzheimer's disease or in other neurodegenerative conditions. Available genomic, transcriptomic and proteomic data from human brains were downloaded from the Mayo Clinic Brain Bank and the Religious Orders Study and Memory and Aging Project. An in-house mouse model of the hippocampal deafferentation/reinnervation was achieved via a stereotaxic lesioning surgery to the entorhinal cortex, and mRNA levels were measured using RNAseq technology. In human temporal cortices, the mean TMEM106B expression was significantly higher in Alzheimer's disease compared to cognitively unimpaired individuals. In the mouse model, hippocampal reached maximum levels during the early phase of reinnervation. These results suggest an active response to tissue damage that is consistent with compensatory synaptic and terminal remodeling.