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.