Unfolded protein response activation in C9orf72 frontotemporal dementia is associated with dipeptide pathology and granulovacuolar degeneration in granule cells.

ABSTRACT: A repeat expansion in the C9orf72 gene is the most prevalent genetic cause of frontotemporal dementia (C9-FTD). Several studies have indicated the involvement of the unfolded protein response (UPR) in C9-FTD. In human neuropathology, UPR markers are strongly associated with granulovacuolar degeneration (GVD). In this study, we aim to assess the presence of UPR markers together with the presence of dipeptide pathology and GVD in post mortem brain tissue from C9-FTD cases and neurologically healthy controls. Using immunohistochemistry we assessed the presence of phosphorylated PERK, IRE1α and eIF2α in the frontal cortex, hippocampus and cerebellum of C9-FTD (n = 18) and control (n = 9) cases. The presence of UPR activation markers was compared with the occurrence of pTDP-43, p62 and dipeptid

SUBMITTER: Gami-Patel P 

PROVIDER: S-EPMC7891436 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature