Τίτλος:
Genotyping and plasma/cerebrospinal fluid profiling of a cohort of frontotemporal dementia–amyotrophic lateral sclerosis patients
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 C9orf72 hexanucleotide repeat expansion analysis, whole exome sequencing and measurement of “classical” (Aβ42, total tau and phospho-tau) and novel (TDP-43) CSF biomarkers and plasma progranulin. Through these analyses, we identified 14 patients with C9orf72 repeat expansion and 11 patients with causative variants in other genes (three in TARDBP, three in GRN, three in VCP, one in FUS, one in SOD1). In ALS patients, we found that levels of phospho-tau were lower in C9orf72 repeat expansion and MAPT c.855C>T (p.Asp285Asp) carriers compared to non-carriers. Additionally, carriers of rare C9orf72 and APP variants had lower levels of total tau and Aβ42, respectively. Plasma progranulin levels were decreased in patients carrying GRN pathogenic variants. This study expands the genotypic and phenotypic spectrum of FTD/ALS and offers insights in possible genotypic/CSF biomarker associations. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Bourbouli, M.
Paraskevas, G.P.
Rentzos, M.
Mathioudakis, L.
Zouvelou, V.
Bougea, A.
Tychalas, A.
Kimiskidis, V.K.
Constantinides, V.
Zafeiris, S.
Tzagournissakis, M.
Papadimas, G.
Karadima, G.
Koutsis, G.
Kroupis, C.
Kartanou, C.
Kapaki, E.
Zaganas, I.
Περιοδικό:
Brain Sciences
Λέξεις-κλειδιά:
amyloid beta protein[1-42]; amyloid precursor protein; guanine nucleotide exchange C9orf72; progranulin; repetitive DNA; superoxide dismutase; TAR DNA binding protein; tau protein; tau181 protein; unclassified drug, adult; aged; amyotrophic lateral sclerosis; Article; cerebrospinal fluid analysis; cohort analysis; disease duration; DNA extraction; enzyme linked immunosorbent assay; female; frontotemporal dementia; gene expression; gene frequency; gene mutation; genetic association; genetic marker; genetic variation; genotype phenotype correlation; genotyping technique; human; major clinical study; male; middle aged; polymerase chain reaction; primary progressive aphasia; prospective study; protein expression; protein fingerprinting; protein phosphorylation; Sanger sequencing; single photon emission computed tomography; trinucleotide repeat; whole exome sequencing
DOI:
10.3390/brainsci11091239
