Peripheral immune profiling in frontotemporal dementia.

Frontotemporal dementia (FTD) encompasses a heterogenous and clinically diverse group of disorders, including the behavioural variant frontotemporal dementia, the non-fluent and the semantic variants of primary progressive aphasia. While these subtypes present with distinct clinical features, emerging evidence implicates neuroinflammation as a shared pathogenic mechanism. Nevertheless, little is known regarding the status of the peripheral immune system in the pathogenesis of FTD. Blood samples were obtained from 27 individuals with a clinical diagnosis of FTD (7 behavioural variants FTD, 10 non-fluent and 10 semantic variants of primary progressive aphasia) and 25 age-matched healthy controls. The immunophenotypes of peripheral immune cell populations were assessed with multicolour flow cytometry. Regulatory T cells were isolated and co-cultured with responder T cells and proliferation was determined by 3H-thymidine incorporation. The immune-related transcriptomic profile of isolated monocytes was analysed using the NanoString Human Inflammation Panel. Plasma levels of inflammatory cytokines and chemokines were quantified using the Olink® Target 48 Cytokine panel. Our analysis demonstrated that the suppressive function of regulatory T cells on responder T cells proliferation was significantly compromised in FTD individuals compared to healthy controls (