Neuron (June 8, 2020) Genetics of Gene Expression in the Aging Human Brain Reveal TDP-43 Proteinopathy Pathophysiology

June 23, 2020

“In this multi-institution collaboration study, Dr. Yang and colleagues analyzed over 750 autopsied human brain samples and discovered and replicated that genetic variants in the TMEM106B and RBFOX1 genes change thousands of brain genes’ expression. The TMEM106B variant they identified was the exact same genetic variant that increases the risk of frontotemporal lobar degeneration (FTLD)-TDP-43 and Limbic-predominant Age-related TDP-43 Encephalopathy (LATE), and therefore their results could reveal a potential mechanism of TMEM106B, an important risk gene of TDP-43 aggregation disorders. In addition, Dr. Yang and colleagues found a lysosomal and myelination gene dysregulation pattern shared between Alzheimer’s disease and LATE, that can potentially explain why many older patients with Alzheimer’s disease pathology also have LATE neuropathological change (i.e., limbic-predominant TDP-43 aggregation).”