| Abstrakt: |
Background: Frontotemporal lobar degeneration (FTLD) describes a neurodegenerative disorder caused by protein accumulation in the brain, with the most common form due to aggregated Tau (FTLD‐tau). A potential role for neuroinflammation in FTLD has been highlighted by the discovery of genetic risk variants related to innate/adaptive immunity. Furthermore, studies have shown increased microglial and astrocyte activation together with T cell infiltration in the brain of a mouse tauopathy model (THY‐Tau22). Methods: To test the possible neuro‐immune interactions in human FTLD‐tau, we obtained FFPE brain tissue from 12 FTLD‐MAPT, 33 Pick's Disease (PiD) and 45 Progressive Supranuclear Palsy (PSP) patients, as well as 55 controls. Using immunohistochemistry we assessed the tau pathology across diseases using antibodies against several sites of tau phosphorylation in association with phenotypic markers of microglia and T cells. Results: Our results show that PiD, PSP and FTLD‐MAPT patients had significantly higher phosphorylated tau protein loads (AT8: p<0.001 for all, AT100: p<0.001 PiD & FTLD‐MAPT, p = 0.009 PSP) compared to controls. We also observed a significant correlation between AT8 and AT100 in all but control groups. Whilst no significant changes were seen between groups in microglial markers (Iba1, CD68 and HLA‐DR), significant associations were seen between AT8 and CD68 in control (r=0.389, p<0.004) and PSP cases (r=0.422, p<0.004), with associations between AT100 and CD68 in PiD (r=0.547, p=0.001) and FTLD‐MAPT (r=0.762, p=0.005). Conclusion: These findings support the involvement of microglia in FTLD, but additional immunophenotyping is necessary for further defining their role in the disease pathogenesis. [ABSTRACT FROM AUTHOR] |
