Cerebrospinal fluid biomarkers in progranulin mutations carriers

Cerebrospinal fluid (CSF) biomarkers (Aβ_1-42, 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.