Amyloid fibrils in FTLD-TDP are composed of TMEM106B and not TDP-43.

ABSTRACT: Frontotemporal lobar degeneration (FTLD) is the third most common neurodegenerative condition after Alzheimer's and Parkinson's diseases¹. FTLD typically presents in 45 to 64 year olds with behavioural changes or progressive decline of language skills². The subtype FTLD-TDP is characterized by certain clinical symptoms and pathological neuronal inclusions with TAR DNA-binding protein (TDP-43) immunoreactivity³. Here we extracted amyloid fibrils from brains of four patients representing four of the five FTLD-TDP subclasses, and determined their structures by cryo-electron microscopy. Unexpectedly, all amyloid fibrils examined were composed of a 135-residue carboxy-terminal fragment of transmembrane protein 106B (TMEM106B), a lysosomal membrane protein previo

SUBMITTER: Jiang YX 

PROVIDER: S-EPMC9844993 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature