A panel of novel astrocytic and synaptic biomarkers in serum and CSF for the differential diagnosis of frontotemporal dementia

Background Frontotemporal dementia (FTD) is the second most common form of presenile dementia. The differential diagnosis of FTD is still a challenging task due to its symptomatic overlap with other neurological diseases and the lack of diagnostic biomarkers. Here, we aimed to investigate the diagnostic potential of novel biomarkers in cerebrospinal fluid (CSF) and blood. Method We included 137 patients from the Centre for Memory Disturbances in Perugia with a diagnosis of FTD (n=37), Alzheimer’s disease (AD, n=47), Parkinson’s Disease (PD, n=14), Dementia with Lewy bodies (DLB, n=8), and cognitively unimpaired patients with other neurological diseases as controls (OND, n=31). All had AD biomarker measurements available. Enzyme‐linked immunosorbent assay (ELISA) or single molecule array (Simoa) were used to quantify the biomarker levels of NPTX2, NPTXR, NfL and GFAP in CSF, as well as NfL and GFAP in serum. Statistical analyses were performed using age and sex corrected analysis of covariance (ANCOVA), generalized linear mixed models (GLMM), ROC analyses, and Spearman correlation coefficients (ρ). Result Differences in protein levels across diagnostic groups were found for NPTX2, NPTXR, NfL (serum and CSF), and GFAP (serum and CSF, figure 1). GLMM predicted NPTX2 and total tau (t‐tau) to best distinguish FTD from OND (p