Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer's Disease from Other Neurological Disorders

Recently, the synaptic proteins neurogranin (Ng) and alpha-synuclein (alpha-Syn) have attracted scientific interest as potential biomarkers for synaptic dysfunction in neurodegenerative diseases. In this study, we measured the CSF Ng and alpha-Syn concentrations in patients affected by AD (n = 69), non-AD neurodegenerative disorders (n-AD = 50) and non-degenerative disorders (n-ND, n = 98). The concentrations of CSF Ng and alpha-Syn were significantly higher in AD than in n-AD and n-ND. Moreover, the A beta 42/Ng and A beta 42/alpha-Syn ratios showed statistically significant differences between groups and discriminated AD patients from n-AD patients, better than Ng or alpha-Syn alone. Regression analyses showed an association of higher Ng concentrations with MMSE < 24, pathological A beta 42/40 ratios, pTau, tTau and the ApoE epsilon 4 genotype. A beta 42/Ng was associated with MMSE < 24, an AD-related FDG-PET pattern, the ApoE epsilon 4 genotype, pathological A beta 42 levels and A beta 42/40 ratios, pTau, and tTau. Moreover, APO-E epsilon 4 carriers showed higher Ng concentrations than non-carriers. Our results support the idea that the A beta 42/Ng ratio is a reliable index of synaptic dysfunction/degeneration able to discriminate AD from other neurological conditions.