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

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The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer's disease. / Öhrfelt, Annika; Brinkmalm, Ann; Dumurgier, Julien; Brinkmalm, Gunnar; Hansson, Oskar; Zetterberg, Henrik; Bouaziz-Amar, Elodie; Hugon, Jacques; Paquet, Claire; Blennow, Kaj.

In: Alzheimer's Research & Therapy, Vol. 8, No. 1, 03.10.2016.

Research output: Contribution to journalArticle

Harvard

Öhrfelt, A, Brinkmalm, A, Dumurgier, J, Brinkmalm, G, Hansson, O, Zetterberg, H, Bouaziz-Amar, E, Hugon, J, Paquet, C & Blennow, K 2016, 'The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer's disease', Alzheimer's Research & Therapy, vol. 8, no. 1. https://doi.org/10.1186/s13195-016-0208-8

APA

CBE

Öhrfelt A, Brinkmalm A, Dumurgier J, Brinkmalm G, Hansson O, Zetterberg H, Bouaziz-Amar E, Hugon J, Paquet C, Blennow K. 2016. The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer's disease. Alzheimer's Research & Therapy. 8(1). https://doi.org/10.1186/s13195-016-0208-8

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Öhrfelt, Annika ; Brinkmalm, Ann ; Dumurgier, Julien ; Brinkmalm, Gunnar ; Hansson, Oskar ; Zetterberg, Henrik ; Bouaziz-Amar, Elodie ; Hugon, Jacques ; Paquet, Claire ; Blennow, Kaj. / The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer's disease. In: Alzheimer's Research & Therapy. 2016 ; Vol. 8, No. 1.

RIS

TY - JOUR

T1 - The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer's disease

AU - Öhrfelt, Annika

AU - Brinkmalm, Ann

AU - Dumurgier, Julien

AU - Brinkmalm, Gunnar

AU - Hansson, Oskar

AU - Zetterberg, Henrik

AU - Bouaziz-Amar, Elodie

AU - Hugon, Jacques

AU - Paquet, Claire

AU - Blennow, Kaj

PY - 2016/10/3

Y1 - 2016/10/3

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Biomarker

KW - Cerebrospinal fluid

KW - Immunopurification

KW - Mass spectrometry

KW - Parallel reaction monitoring

KW - Selected reaction monitoring

KW - Synaptotagmin

UR - http://www.scopus.com/inward/record.url?scp=84990818526&partnerID=8YFLogxK

U2 - 10.1186/s13195-016-0208-8

DO - 10.1186/s13195-016-0208-8

M3 - Article

VL - 8

JO - Alzheimer's Research & Therapy

T2 - Alzheimer's Research & Therapy

JF - Alzheimer's Research & Therapy

SN - 1758-9193

IS - 1

ER -