Cerebrospinal fluid levels of SNAP‐25 and SYT1 in Alzheimer’s and Parkinson’s disease

Abstract

AbstractBackgroundDisease‐related synaptic pathologies are common in neurodegenerative diseases, e.g. Alzheimer’s disease (AD), and Parkinson’s disease (PD). In AD, synapse loss appears to occur earlier in the disease process than the plaques or tangles and is more strongly correlated with cognitive decline. Recently it has become possible to study synaptic loss by quantifying synaptic proteins directly in cerebrospinal fluid (CSF). Increased CSF levels of the postsynaptic protein Neurogranin (Ng) in patients with AD or mild cognitive impairment have been shown in several studies. Interestingly, increased CSF Ng levels have not been observed in PD and other neurodegenerative diseases. Significantly elevated CSF levels of the presynaptic proteins GAP‐43, SNAP‐25, and synaptotagmin‐1 (SYT1) have also been found in patients with AD and MCI compared with controls. However, these studies need to be independently replicated in larger and more diverse cohorts, including other neurodegenerative diseases.MethodWe measured the CSF levels of SNAP‐25 and SYT1 in the prospective Swedish BioFINDER study, which included 1282 subjects, of which 553 were Ab‐negative controls, 195 Ab‐positive controls, 110 Ab‐negative cases with MCI, 137 Ab‐positive cases with MCI, 152 cases with AD with dementia and 135 cases with PD.ResultSNAP‐25 concentration in CSF was increased in AD patients with dementia compared with Ab‐negative controls and MCI patients (p<0.0001), but also compared with Ab‐positive controls. Further, the levels were also increased in Ab‐positive controls and Ab‐positive MCI patients compared with Ab‐negative controls (p<0.0001). In PD, there was a non‐significant trend to decreased levels compared to controls. SYT1 in CSF was increased in AD patients compared with Ab‐negative controls and MCI patients (p<0.0001). The levels were also increased in Ab‐positive controls (p<0.0001) and Ab‐positive cases with MCI compared with Ab‐negative controls (p <0.05). The levels were decreased in PD compared with controls (p <0.05). Group comparison of SNAP‐25 and SYT1 levels. (*p <= 0.05, ****: p <= 0.0001) are shown in figures.ConclusionCSF SNAP‐25 and SYT1 concentrations increase already during the preclinical stages of AD, and SNAP‐25 was further increased in AD dementia. In PD, the levels were decreased, especially for SYT1.