Markers of astrocyte glutamate cycling function were reduced in FTLD-tau ( P = 0.0075 Pick’s disease: P < 0.0400) implying astrocyte reactivity associated with a decreased glutamate cycling activity, which was further associated with pTau expression. GFAP expression was increased in FTLD-tau ( P = 0.0345) with the highest expression in Pick’s disease ( P = 0.0019), while ALDH1L1 was unchanged. However, several associations were detected between pTau epitopes and microglia, supporting an interplay between them. The only microglial marker increased in FTLD-tau was CD16 ( P = 0.0292) and specifically in FTLD-MAPT cases ( P = 0.0150). Progressive supranuclear palsy with frontotemporal dementia consistently had a lower pTau protein load compared to Pick’s disease across tau epitopes. pSer356 expression was greatest in FTLD-MAPT cases versus controls ( P < 0.0001), whereas the expression of other markers was highest in Pick’s disease. The adaptive immune response was explored via CD4 + and CD8 + T cell quantification and the neuroinflammatory environment was investigated via the expression of 30 inflammatory-related proteins using V-Plex Meso Scale Discovery.Īs expected, all pTau markers were increased in FTLD-tau cases compared to controls. The immunophenotypes of microglia and astrocytes were assessed with phenotypic markers (Iba1, CD68, HLA-DR, CD64, CD32a, CD16 for microglia and GFAP, EAAT2, glutamine synthetase and ALDH1L1 for astrocytes). Tau pathology was assessed in the cerebral cortex using antibodies directed against: Tau-2 (phosphorylated and unphosphorylated tau), AT8 (pSer202/pThr205), AT100 (pThr212/pSer214), CP13 (pSer202), PHF1 (pSer396/pSer404), pThr181 and pSer356. We conducted a detailed post-mortem study of FTLD-tau cases including 45 progressive supranuclear palsy with clinical frontotemporal dementia, 33 Pick’s disease, 12 FTLD-MAPT and 52 control brains to characterize the link between phosphorylated tau (pTau) epitopes and the innate and adaptive immunity. However, this remains to be confirmed in FTLD-tau patients. Studies have shown microglial and astrocyte activation together with T cell infiltration in the brain of THY-Tau22 tauopathy mice. Identification of genetic risk variants related to innate/adaptive immunity have highlighted a role for neuroinflammation and neuroimmune interactions in FTLD. Frontotemporal lobar degeneration with tau (FTLD-tau) is a group of tauopathies that underlie ∼50% of FTLD cases.
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