Progranulin Protein Levels in Cerebrospinal Fluid in Primary Neurodegenerative Dementias

Article type: Research Article

Authors: Morenas-Rodríguez, Estrella^{a; b} | Cervera-Carles, Laura^{a; b} | Vilaplana, Eduard^{a; b} | Alcolea, Daniel^{a; b} | Carmona-Iragui, María^{a; b} | Dols-Icardo, Oriol^{a; b} | Ribosa-Nogué, Roser^{a; b} | Muñoz-Llahuna, Laia^{a; b} | Sala, Isabel^{a; b} | Belén Sánchez-Saudinós, M.^{a; b} | Blesa, Rafael^{a; b} | Clarimón, Jordi^{a; b} | Fortea, Juan^{a; b} | Lleó, Alberto^{a; b; *}

Affiliations: [a] Memory Unit, Department of Neurology, Institut d’Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain | [b] Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain

Correspondence: [*] Correspondence to: Alberto Lleó, MD, PhD, Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau Sant Antoni M^a Claret 167 Barcelona 08025, Spain. Tel.: +34 93 556 59 86; Fax: +34 93 556 56 02; E-mail: [email protected].

Abstract: Background:Progranulin is implicated in frontotemporal dementia (FTD), but its role in other neurodegenerative disorders is unknown. Objective:To investigate the levels of progranulin (PGRN) in cerebrospinal fluid (CSF) in different neurodegenerative dementias and their correlation with levels in plasma in cognitively normal subjects. Methods:We measured PGRN in CSF in 229 patients with amnestic mild cognitive impairment, Alzheimer’s disease dementia, sporadic FTD, dementia with Lewy bodies, corticobasal syndrome, or progressive supranuclear palsy. We also measured PGRN in CSF and plasma in 74 cognitively normal individuals. We examined the correlation between PGRN levels in CSF and diagnosis, cortical thickness, genetic factors and other CSF biomarkers. We also investigated the correlation between plasma and CSF levels of PGRN in cognitively normal individuals. Results:CSF levels did not differ across diagnoses or correlate with cortical thickness. Polymorphism rs5848 in GRN influenced CSF PGRN levels, but APOE ɛ4 allele did not. Amyloid-β42, t-tau, p-tau, and YKL-40 levels correlated weakly with PGRN in CSF. We found a weak correlation (r = 0.362) between plasma and CSF PGRN levels in cognitively normal individuals. Conclusions:Our findings do not support a diagnostic value of CSF PGRN in neurodegenerative diseases. Our data confirm that levels of PGRN in plasma do not reflect accurately levels in CSF in cognitively normal controls. These data should be considered in clinical trials aiming to increase PGRN.

Keywords: Alzheimer’s disease, amyloid-β, biomarker, cerebrospinal fluid, dementia, plasma, progranulin, tau

DOI: 10.3233/JAD-150746

Journal: Journal of Alzheimer's Disease, vol. 50, no. 2, pp. 539-546, 2016