Amyloid-β42/Neurogranin Ratio as a Potential Index for Cognitive Impairment in Parkinson's Disease

Synaptopathy is critical in pathophysiology of Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of neurogranin (NG) and amyloid-β42 (Aβ42) are considered markers of synaptic dysfunction in neurodegenerative diseases.

To evaluate the CSF synaptopathy-related biomarkers, especially the novel Aβ42/NG ratio, in PD, establishing possible associations with cognitive level and other clinical parameters.

Levels of NG, Aβ42, amyloid-β40, total and phosphorylated tau, and Aβ42/NG ratio were measured in 30 PD patients and 30 controls and correlated with cognitive and motor parameters. The accuracy in distinguishing the cognitive status was determined.

NG and Aβ42 were significantly reduced in PD, with higher NG levels in patients with worse cognition. The Aβ42/NG ratio showed a direct correlation with Mini-Mental State Examination, independently from age and sex, and differentiated cognitively impaired patients with 92% sensitivity and 71.4% specificity, accuracy higher than NG alone. No correlations resulted with motor disturbances or therapy.

The novel Aβ42/NG ratio couples either presynaptic or postsynaptic markers of synaptic dysfunction, representing a potential global index of synaptopathy, useful to track cognitive functions in PD.