P1‐010: Quantification of the synaptic protein neurogranin in cerebrospinal fluid across different neurodegenerative diseases: A selective Alzheimer's disease biomarker?

Synapses are integral to the molecular processes underlying learning and memory. There is substantial evidence that loss of synapses and dysfunction in synaptic plasticity precede cell death and cognitive decline in Alzheimer's disease (AD). Further, cognitive decline is best correlated with synapse loss rather than the deposition of amyloid-β (Aβ). The identification of new synaptic biomarkers will improve diagnosis in the pre-symptomatic and prodromal stages of AD, aid understanding about pathological processes and contribute information about biochemical effectiveness of treatment in clinical trials. In this study we look at the levels of neurogranin (Ng), a post-synaptic protein, in cerebrospinal (CSF) from patients with a range of neurodegenerative diseases and assessed its effectiveness as a specific AD biomarker. We used a novel ELISA assay to analyse CSF Ng. Altogether 400 subjects donated CSF during clinical investigation, including controls (n=26), patients with AD (n = 142), frontotemporal dementia (FTD) (n = 45), Parkinson's disease (PD) ( n= 31), Lewy body dementia (LBD) (n = 13), vascular dementia (VaD) (n = 7), progressive supranuclear palsy (PSP) (n = 47), multiple system atrophy (MSA) (n=31), neurodegeneration with unclear diagnosis (n=10) and patients with mood disorder (n = 48). Ng levels between groups were compared using Kruskal Wallis test and Dunns multiple comparisons test. Spearman's correlation was performed to look at the association of Ng with Total-tau (T-tau) and phospho-tau (P-tau). Statistical significance was set at P<0.05. We show a significant increase in CSF Ng levels in AD patients compared to controls (P<0.01). We found no difference in Ng levels in the other neurodegenerative groups compared to controls. In addition, we found a positive correlation between Ng and T-tau as well as Ng and P-tau in AD patients (P= <0.001; P= <0.001 respectively). These results confirm an increase in Ng in AD patients as previously reported. We show for the first time that Ng is not significantly elevated in other neurodegenerative diseases including patients with predominant tau pathology (PSP and FTD) as well as those with synucleinopathies (PD and LBD). This suggests that Ng could be a selective AD biomarker.