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A Novel ELISA for the Measurement of Cerebrospinal Fluid SNAP-25 in Patients with Alzheimer’s Disease

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Synaptic degeneration is central in Alzheimer's disease (AD) pathogenesis and biomarkers to monitor this pathophysiology in living patients are warranted. We developed a novel sandwich enzyme-linked immunosorbent assay (ELISA) for… Click to show full abstract

Synaptic degeneration is central in Alzheimer's disease (AD) pathogenesis and biomarkers to monitor this pathophysiology in living patients are warranted. We developed a novel sandwich enzyme-linked immunosorbent assay (ELISA) for the measurement of the pre-synaptic protein SNAP-25 in cerebrospinal fluid (CSF) and evaluated it as a biomarker for AD. CSF samples included a pilot study consisting of AD (N = 26) and controls (N = 26), and two independent clinical cohorts of AD patients and controls. Cohort I included CSF samples from patients with dementia due to AD (N = 17), patients with mild cognitive impairment (MCI) due to AD (N = 5) and controls (N = 17), and cohort II CSF samples from patients with dementia due to AD (N = 24), patients with MCI due to AD (N = 18) and controls (N = 36). CSF levels of SNAP-25 were significantly increased in patients with AD compared with controls (P ≤ 0.00001). In both clinical cohorts, CSF levels of SNAP-25 were significantly increased in patients with MCI due to AD (P < 0.0001). SNAP-25 could differentiate dementia due to AD (N = 41) from controls (N = 52) and MCI due to AD (N = 23) from controls (N = 52) with areas under the curve of 0.967 (P < 0.0001) and 0.948 (P < 0.0001), respectively. CSF SNAP-25 is a promising AD biomarker that differentiates AD patients in different clinical stages of the disease from controls with excellent diagnostic accuracy. Future studies should address the specificity of the CSF SNAP-25 against common differential diagnoses to AD, as well as how the biomarker changes in response to treatment with disease-modifying drug candidates.

Keywords: snap; alzheimer disease; disease; csf; elisa measurement; cerebrospinal fluid

Journal Title: Neuroscience
Year Published: 2019

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