CSF angiogenin levels in amyotrophic lateral Sclerosis-Frontotemporal dementia spectrum

Objective: Angiogenin (ANG) is a pro-angiogenic and neurotrophic factor with an important role
in stress-induced injury, by promoting neovascularization and neuronal survival. Identification of
loss-of-function mutations and evidence of beneficial effect of ANG administration in transgenic
SOD1G93A mice have linked ANG to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS),
stimulating interest in considering circulating ANG levels as an ALS disease biomarker although
robust evidence is still lacking. Aim of our study was to assess differences of ANG levels in the
cerebrospinal fluid (CSF) of a large cohort of patients with ALS and frontotemporal dementia
(FTD) compared to controls and to explore correlations between ANG content and disease-related
clinical variables.
Methods: ANG levels were measured in CSF samples using a commercially available ELISA kit in
88 patients affected with ALS and/or FTD and 46 unrelated individuals (control group).
Results: ANG levels didn’t differ significantly between cases and controls. Patients with FTD or
ALS-FTD showed significantly increased CSF concentration of ANG compared to ALS patients
without dementia and controls in a multivariate regression model (p<0.001). No correlations were
found in ALS/FTD patients between ANG levels and clinical parameters, including age, presence of
C9orf72 repeat expansion, body mass index (BMI).
Conclusions: our findings highlight a role of ANG as CSF biomarker useful to identify ALS
patients with concurrent FTD and suggest that it should be further explored as potential biomarker
for FTD.