Serum C-Peptide, Visfatin, Resistin, and Ghrelin are Altered in Sporadic and GRN-Associated Frontotemporal Lobar Degeneration

Article type: Research Article

Authors: Zanardini, Roberta^{a; 1} | Benussi, Luisa^{a; 1} | Fostinelli, Silvia^a | Saraceno, Claudia^a | Ciani, Miriam^{a; b} | Borroni, Barbara^c | Padovani, Alessandro^c | Binetti, Giuliano^{a; d} | Ghidoni, Roberta^{a; *}

Affiliations: [a] Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [b] Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy | [c] Department of Clinical and Experimental Sciences, Neurology Unit, University of Brescia, Brescia, Italy | [d] MAC Memory Center, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

Correspondence: [*] Correspondence to: Roberta Ghidoni, Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, via Pilastroni 4, Brescia, I-25125, Italy. Tel.: +0039 030 3501725; Fax: +0039 030 3533513; E-mail: rghidoni@fatebenefratelli.eu.

Note: [1] These authors contributed equally to this work.

Abstract: Frontotemporal lobar degeneration (FTLD) is a group of complex neurodegenerative disease characterized by progressive deterioration of the frontal and anterior temporal lobes of the brain resulting in different heterogeneous conditions, mainly characterized by personality changes, behavioral disturbances, such as binge eating, and deficits in language and executive functions. Null mutations in progranulin gene (GRN) are one of the most frequent genetic determinants in familial frontotemporal dementia. Recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance revealing its metabolic function. Increasing evidence suggests that neurodegenerative dementias are associated with a higher prevalence of metabolic changes than in the general population. According to these findings, the aim of this study is to investigate putative alterations in markers linked to metabolic functions (i.e., C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, glucagon, insulin, resistin, and three adipokines as visfatin, leptin, and plasminogen activator inhibitor-1 total) in sporadic and GRN-related FTLD. We found that 1) C-peptide is increased in sporadic and GRN-mutated FTLD patients; in addition, we demonstrated an anticipation of the disease in patients with the highest C-peptide concentrations; 2) visfatin is slightly reduced in the whole FTLD group; 3) resistin, an adipokine involved in inflammatory-related diseases, is specifically increased in FTLD due to GRN null mutations; 4) ghrelin concentration is specifically increased in pre-symptomatic subjects and FTLD patients with GRN mutations. These findings support the hypothesis that alterations in metabolic pattern are involved in FTLD progression highlighting novel putative targets for the development of preventive and personalized therapies.

Keywords: Adipokines, C-peptide, FTLD, ghrelin, haploinsufficiency, resistin, serum, visfatin

DOI: 10.3233/JAD-170747

Journal: Journal of Alzheimer's Disease, vol. 61, no. 3, pp. 1053-1060, 2018