TYK2 as a novel therapeutic target in Alzheimer's Disease with TDP-43 inclusions.

ABSTRACT: Neuroinflammation is a pathological feature of many neurodegenerative diseases, including Alzheimer's disease (AD)^1,2 and amyotrophic lateral sclerosis (ALS)³, raising the possibility of common therapeutic targets. We previously established that cytoplasmic double-stranded RNA (cdsRNA) is spatially coincident with cytoplasmic pTDP-43 inclusions in neurons of patients with C9ORF72-mediated ALS⁴. CdsRNA triggers a type-I interferon (IFN-I)-based innate immune response in human neural cells, resulting in their death⁴. Here, we report that cdsRNA is also spatially coincident with pTDP-43 cytoplasmic inclusions in brain cells of patients with AD pathology and that type-I interferon response genes are significantly upregulated in brain regions affected

SUBMITTER: Konig LE 

PROVIDER: S-EPMC11185596 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature