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Open Access 01-12-2016 | Research

The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer’s disease

Authors: Annika Öhrfelt, Ann Brinkmalm, Julien Dumurgier, Gunnar Brinkmalm, Oskar Hansson, Henrik Zetterberg, Elodie Bouaziz-Amar, Jacques Hugon, Claire Paquet, Kaj Blennow

Published in: Alzheimer's Research & Therapy | Issue 1/2016

Abstract

Background

Synaptic degeneration is a central pathogenic event in Alzheimer’s disease that occurs early during the course of disease and correlates with cognitive symptoms. The pre-synaptic vesicle protein synaptotagmin-1 appears to be essential for the maintenance of an intact synaptic transmission and cognitive function. Synaptotagmin-1 in cerebrospinal fluid is a candidate Alzheimer biomarker for synaptic dysfunction that also may correlate with cognitive decline.

Methods

In this study, a novel mass spectrometry-based assay for measurement of cerebrospinal fluid synaptotagmin-1 was developed, and was evaluated in two independent sample sets of patients and controls. Sample set I included cerebrospinal fluid samples from patients with dementia due to Alzheimer’s disease (N = 17, age 52–86 years), patients with mild cognitive impairment due to Alzheimer’s disease (N = 5, age 62–88 years), and controls (N = 17, age 41–82 years). Sample set II included cerebrospinal fluid samples from patients with dementia due to Alzheimer’s disease (N = 24, age 52–84 years), patients with mild cognitive impairment due to Alzheimer’s disease (N = 18, age 58–83 years), and controls (N = 36, age 43–80 years).

Results

The reproducibility of the novel method showed coefficients of variation of the measured synaptotagmin-1 peptide 215–223 (VPYSELGGK) and peptide 238–245 (HDIIGEFK) of 14 % or below. In both investigated sample sets, the CSF levels of synaptotagmin-1 were significantly increased in patients with dementia due to Alzheimer’s disease (P ≤ 0.0001) and in patients with mild cognitive impairment due to Alzheimer’s disease (P < 0.001). In addition, in sample set I the synaptotagmin-1 level was significantly higher in patients with mild cognitive impairment due to Alzheimer’s disease compared with patients with dementia due to Alzheimer’s disease (P ≤ 0.05).

Conclusions

Cerebrospinal fluid synaptotagmin-1 is a promising biomarker to monitor synaptic dysfunction and degeneration in Alzheimer’s disease that may be useful for clinical diagnosis, to monitor effect on synaptic integrity by novel drug candidates, and to explore pathophysiology directly in patients with Alzheimer’s disease.

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Title: The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer’s disease
Authors: Annika Öhrfelt
Ann Brinkmalm
Julien Dumurgier
Gunnar Brinkmalm
Oskar Hansson
Henrik Zetterberg
Elodie Bouaziz-Amar
Jacques Hugon
Claire Paquet
Kaj Blennow
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Alzheimer's Research & Therapy / Issue 1/2016
Electronic ISSN: 1758-9193
DOI: https://doi.org/10.1186/s13195-016-0208-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer’s disease

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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