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Alzheimer-s Research and Therapy

, 8:41

First Online: 03 October 2016Received: 07 July 2016Accepted: 05 September 2016

Abstract

BackgroundSynaptic 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.

MethodsIn 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.

ResultsThe 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.

ConclusionsCerebrospinal 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.

KeywordsAlzheimer’s disease Biomarker Cerebrospinal fluid Synaptotagmin Mass spectrometry Immunopurification Selected reaction monitoring Parallel reaction monitoring AbbreviationsCVCoefficients of variation

CSFCerebrospinal fluid

MCIMild cognitive impairment

MMSEMini-Mental State Examination

PBSPhosphate-buffered saline

SNAP-25Synaptosomal-associated protein 25

ROCReceiver operating characteristic

Electronic supplementary materialThe online version of this article doi:10.1186-s13195-016-0208-8 contains supplementary material, which is available to authorized users.

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Autor: Annika Öhrfelt - Ann Brinkmalm - Julien Dumurgier - Gunnar Brinkmalm - Oskar Hansson - Henrik Zetterberg - Elodie Bouaziz-

Fuente: https://link.springer.com/article/10.1186/s13195-016-0208-8







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