L’Extatique_75 (@extatique75.bsky.social)

An acetylated Tau-174 CSF biomarker discriminates between TDP-43 and tau pathology in patients with frontotemporal lobar degeneration | Nature Medicine Biomarkers to determine underlying frontotemporal lobar degeneration (FTLD) tau or TAR DNA-binding protein (TDP) pathology during life are needed to advance clinical trials targeting specific FTD pathologies. For this purpose, we developed a new ultrasensitive immunoassay to quantify acetylated tau at lysine 174 (AcTau174) in cerebrospinal fluid (CSF). In a sporadic cohort (n = 513), AcTau174 concentrations were higher in all dementia groups (FTLD-TDP, FTLD-Tau, Alzheimer’s disease (AD), mild cognitive impairment (MCI)-AD and dementia with Lewy bodies (DLB)) compared to controls. The largest increase was observed in the FTLD-TDP group, particularly patients with semantic variant primary progressive aphasia (svPPA) and GRN mutation carriers. Notably, AcTau174 discriminated FTLD-TDP from FTLD-Tau (area under the curve (AUC) = 0.83, 95% confidence interval (CI) = 0.75–0.91) and FTLD-TDP from controls (AUC = 0.95, 95% CI = 0.92–0.99) with high accuracy. This was replicated in independent, https://doi.org/10.1038/s41591-026-04341-6