The synaptic biomarker contactin5 differentiates between neurodegenerative dementias

Abstract

AbstractBackgroundSynapses are crucial for memory formation, and their disruption is among the earliest events in Alzheimer’s disease (AD) pathogenesis. Less is known about synaptic alterations in other types of dementia. Contactin5 (CNTN‐5) is a synaptic protein and one of the neural adhesion molecules. It contributes to synaptic formation, plasticity and is associated with dendritic morphogenesis. A GWAS identified a risk variant (rs 141684 G) in CNTN‐5 gene, which is associated with increased risk of AD development. We aimed to assess whether CNTN‐5 could be a differential diagnostic cerebrospinal fluid (CSF) biomarker for AD from other types of dementia.MethodCNTN‐5 levels in CSF samples were measured with two methods: an in‐house developed immunoassay on the automated ELLA platform, and a multiple reaction monitoring mass spectrometry (MRM) assay. The clinical cohort included controls (n = 27), patients with AD (n = 19), patients with behavioral variant frontotemporal dementia (bvFTD) (n = 18), and patients with dementia with Lewy bodies and Parkinson’s disease dementia (PDD/DLB) (n = 18; table 1). CNTN‐5 results obtained with both methods were correlated using spearman’s correlation. Differences in CNTN‐5 levels between the diagnostic groups were assessed with Kruskal‐Wallis test and corrected with Dunn´s factor for multiple comparison.ResultsAs shown in Figure 1, CNTN‐5 measurements between methods were strongly and positively correlated (rho = 0.58, p<0.001). In AD patients, CNTN‐5 levels were significantly elevated in comparison to bvFTD patients with both assays (both: p<0.05), as well as, compared to patients with DLB/PDD (MRM: p<0.05 and ELLA: p<0.01). There was no significant difference in CNTN‐5 levels between AD and controls, or between bvFTD and PDD/DLB, as shown in figure 2.ConclusionOur results showed that elevated CNTN‐5 is a promising synaptic biomarker, with specificity for AD. As a next step, we would look further into a larger clinical cohort, where associations between CNTN‐5 levels and cognitive stage could be thoroughly studied.