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

Annika Öhrfelt; Ann Brinkmalm; Julien Dumurgier; Henrik Zetterberg; Elodie Bouaziz-Amar; Jacques Hugon; Claire Paquet; Kaj Blennow

doi:10.1016/j.neuroscience.2018.11.038

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

Neuroscience. 2019 Nov 10:420:136-144. doi: 10.1016/j.neuroscience.2018.11.038. Epub 2018 Dec 5.

Authors

Annika Öhrfelt¹, Ann Brinkmalm², Julien Dumurgier³, Henrik Zetterberg⁴, Elodie Bouaziz-Amar⁵, Jacques Hugon⁶, Claire Paquet⁷, Kaj Blennow⁸

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. Electronic address: [email protected].
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. Electronic address: [email protected].
³ Centre de Neurologie Cognitive CMRR Paris Nord Ile de France, INSERM UMR-S942, Groupe Hospitalier Lariboisière Fernand-Widal Saint-Louis, Paris, France.
⁴ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom; UK Dementia Research Institute, London, United Kingdom. Electronic address: [email protected].
⁵ Service de Biochimie, Groupe Hospitalier Lariboisiere FW Saint-Louis, APHP, Université Paris Diderot, 75010 Paris, France. Electronic address: [email protected].
⁶ Centre de Neurologie Cognitive CMRR Paris Nord Ile de France, INSERM UMR-S942, Groupe Hospitalier Lariboisière Fernand-Widal Saint-Louis, Paris, France. Electronic address: [email protected].
⁷ Centre de Neurologie Cognitive CMRR Paris Nord Ile de France, INSERM UMR-S942, Groupe Hospitalier Lariboisière Fernand-Widal Saint-Louis, Paris, France. Electronic address: [email protected].
⁸ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. Electronic address: [email protected].

PMID: 30528858
DOI: 10.1016/j.neuroscience.2018.11.038

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: Alzheimer’s disease; ELISA; SNAP-25; biomarker; cerebrospinal fluid; mild cognitive impairment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease / cerebrospinal fluid*
Biomarkers / cerebrospinal fluid*
Enzyme-Linked Immunosorbent Assay / methods*
Female
Humans
Male
Sensitivity and Specificity
Synaptosomal-Associated Protein 25 / cerebrospinal fluid*

Substances

Biomarkers
SNAP25 protein, human
Synaptosomal-Associated Protein 25