title: Cerebrospinal fluid biomarkers in Progranulin mutations carriers.
abstract: Cerebrospinal fluid (CSF) biomarkers (Aβ₁₋₄₂, total tau, P-181 tau) are currently used to support a clinical diagnosis of Alzheimer's disease (AD). The CSF profile in frontotemporal lobar degeneration (FTLD) caused by Progranulin (GRN) mutation is unknown. We assessed CSF biomarkers in 145 AD, 140 FTLD (20 GRN positive, 120 GRN negative) patients, and 38 controls. Taking into account the reference values used in clinical practice, GRN mutation carriers and controls did not differ significantly for any biomarker, whereas GRN negative FTLD patients had higher tau levels than controls (p < 0.001) and patients carrying GRN Thr272fs mutation (p = 0.033, Chi-Square test). Comparing CSF biomarkers mean values among groups, total tau was significantly increased in GRN negative FTLD and in mutation carriers compared with controls (p < 0.001). P-181 tau CSF was increased in AD patients and in GRN negative FTLD compared with controls (p < 0.001), but not in 17 patients carrying the Thr272fs mutation. 88.2% of mutation carriers had normal CSF tau, despite the neurodegenerative nature of FTLD. Our results suggest that GRN mutation carriers have normal or borderline CSF biomarkers. In patients with an AD-like phenotype but normal or borderline CSF biomarkers, a diagnosis of FTLD-U caused by GRN mutations should be considered.
authors: Department of Neurology, Amedeo Avogadro University, Novara, Italy. mcarecchio@gmail.com
authors: Miryam
authors: M
authors: Carecchio
authors: Chiara
authors: C
authors: Fenoglio
authors: Francesca
authors: F
authors: Cortini
authors: Cristoforo
authors: C
authors: Comi
authors: Luisa
authors: L
authors: Benussi
authors: Roberta
authors: R
authors: Ghidoni
authors: Barbara
authors: B
authors: Borroni
authors: Milena
authors: M
authors: De Riz
authors: Maria
authors: M
authors: Serpente
authors: Claudia
authors: C
authors: Cantoni
authors: Massimo
authors: M
authors: Franceschi
authors: Valentina
authors: V
authors: Albertini
authors: Francesco
authors: F
authors: Monaco
authors: Innocenzo
authors: I
authors: Rainero
authors: Giuliano
authors: G
authors: Binetti
authors: Alessandro
authors: A
authors: Padovani
authors: Nereo
authors: N
authors: Bresolin
authors: Elio
authors: E
authors: Scarpini
authors: Daniela
authors: D
authors: Galimberti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000134:cerebrospinal fluid* / Q000150:complications / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D000077153:Progranulins; D013223:Statistics as Topic; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D000077153:Progranulins; C075222:amyloid beta-protein (1-42); D016875:tau Proteins