Virginia Estades Ayuso, Sarah Pickles, Tiffany Todd, Mei Yue, Karen Jansen-West, Yuping Song, Jesús González Bejarano, Bailey Rawlinson, Michael DeTure, Neill R Graff-Radford, Bradley F Boeve, David S Knopman, Ronald C Petersen, Dennis W Dickson, Keith A Josephs, Leonard Petrucelli, Mercedes Prudencio
BACKGROUND: Inclusions of TAR DNA-binding protein 43 kDa (TDP-43) has been designated limbic-predominant, age-related TDP-43 encephalopathy (LATE), with or without co-occurrence of Alzheimer's disease (AD). Approximately, 30-70% AD cases present TDP-43 proteinopathy (AD-TDP), and a greater disease severity compared to AD patients without TDP-43 pathology. However, it remains unclear to what extent TDP-43 dysfunction is involved in AD pathogenesis. METHODS: To investigate whether TDP-43 dysfunction is a prominent feature in AD-TDP cases, we evaluated whether non-conserved cryptic exons, which serve as a marker of TDP-43 dysfunction in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP), accumulate in AD-TDP brains...
August 21, 2023: Molecular Neurodegeneration