Genotyping and Plasma/Cerebrospinal Fluid Profiling of a Cohort of Frontotemporal Dementia-Amyotrophic Lateral Sclerosis Patients.

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are part of the same pathophysiological spectrum and have common genetic and cerebrospinal fluid (CSF) biomarkers. Our aim here was to identify causative gene variants in a cohort of Greek patients with FTD, ALS and FTD-ALS, to measure levels of CSF biomarkers and to investigate genotype-phenotype/CSF biomarker associations. In this cohort of 130 patients (56 FTD, 58 ALS and 16 FTD-ALS), we performed hexanucleotide repeat expansion analysis, whole exome sequencing and measurement of "classical" (Aβ, total tau and phospho-tau) and novel (TDP-43) CSF biomarkers and plasma progranulin. Through these analyses, we identified 14 patients with repeat expansion and 11 patients with causative variants in other genes (three in , three in , three in , one in , one in ). In ALS patients, we found that levels of phospho-tau were lower in repeat expansion and c.855C>T (p.Asp285Asp) carriers compared to non-carriers. Additionally, carriers of rare and variants had lower levels of total tau and Aβ, respectively. Plasma progranulin levels were decreased in patients carrying pathogenic variants. This study expands the genotypic and phenotypic spectrum of FTD/ALS and offers insights in possible genotypic/CSF biomarker associations.