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SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer's disease

Brinkmalm, Ann; Brinkmalm, Gunnar; Honer, William G.; Frolich, Lutz; Hausner, Lucrezia; Minthon, Lennart LU ; Hansson, Oskar LU ; Wallin, Anders; Zetterberg, Henrik and Blennow, Kaj, et al. (2014) In Molecular Neurodegeneration 9.
Abstract
Background: Synaptic degeneration is an early pathogenic event in Alzheimer's disease, associated with cognitive impairment and disease progression. Cerebrospinal fluid biomarkers reflecting synaptic integrity would be highly valuable tools to monitor synaptic degeneration directly in patients. We previously showed that synaptic proteins such as synaptotagmin and synaptosomal-associated protein 25 (SNAP-25) could be detected in pooled samples of cerebrospinal fluid, however these assays were not sensitive enough for individual samples. Results: We report a new strategy to study synaptic pathology by using affinity purification and mass spectrometry to measure the levels of the presynaptic protein SNAP-25 in cerebrospinal fluid. By applying... (More)
Background: Synaptic degeneration is an early pathogenic event in Alzheimer's disease, associated with cognitive impairment and disease progression. Cerebrospinal fluid biomarkers reflecting synaptic integrity would be highly valuable tools to monitor synaptic degeneration directly in patients. We previously showed that synaptic proteins such as synaptotagmin and synaptosomal-associated protein 25 (SNAP-25) could be detected in pooled samples of cerebrospinal fluid, however these assays were not sensitive enough for individual samples. Results: We report a new strategy to study synaptic pathology by using affinity purification and mass spectrometry to measure the levels of the presynaptic protein SNAP-25 in cerebrospinal fluid. By applying this novel affinity mass spectrometry strategy on three separate cohorts of patients, the value of SNAP-25 as a cerebrospinal fluid biomarker for synaptic integrity in Alzheimer's disease was assessed for the first time. We found significantly higher levels of cerebrospinal fluid SNAP-25 fragments in Alzheimer's disease, even in the very early stages, in three separate cohorts. Cerebrospinal fluid SNAP-25 differentiated Alzheimer's disease from controls with area under the curve of 0.901 (P < 0.0001). Conclusions: We developed a sensitive method to analyze SNAP-25 levels in individual CSF samples that to our knowledge was not possible previously. Our results support the notion that synaptic biomarkers may be important tools for early diagnosis, assessment of disease progression, and to monitor drug effects in treatment trials. (Less)
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publication status
published
subject
keywords
Alzheimer's disease, Biomarker, Cerebrospinal fluid, SNAP-25, SNARE, proteins, Mass spectrometry, Immunopurification, Selected reaction, monitoring
in
Molecular Neurodegeneration
volume
9
publisher
BioMed Central
external identifiers
  • wos:000345935000001
  • scopus:84990967378
ISSN
1750-1326
DOI
10.1186/1750-1326-9-53
language
English
LU publication?
yes
id
365c8c8c-d29b-4e55-8659-b3df98f0ede1 (old id 4962744)
date added to LUP
2015-02-03 07:03:27
date last changed
2017-11-19 03:41:13
@article{365c8c8c-d29b-4e55-8659-b3df98f0ede1,
  abstract     = {Background: Synaptic degeneration is an early pathogenic event in Alzheimer's disease, associated with cognitive impairment and disease progression. Cerebrospinal fluid biomarkers reflecting synaptic integrity would be highly valuable tools to monitor synaptic degeneration directly in patients. We previously showed that synaptic proteins such as synaptotagmin and synaptosomal-associated protein 25 (SNAP-25) could be detected in pooled samples of cerebrospinal fluid, however these assays were not sensitive enough for individual samples. Results: We report a new strategy to study synaptic pathology by using affinity purification and mass spectrometry to measure the levels of the presynaptic protein SNAP-25 in cerebrospinal fluid. By applying this novel affinity mass spectrometry strategy on three separate cohorts of patients, the value of SNAP-25 as a cerebrospinal fluid biomarker for synaptic integrity in Alzheimer's disease was assessed for the first time. We found significantly higher levels of cerebrospinal fluid SNAP-25 fragments in Alzheimer's disease, even in the very early stages, in three separate cohorts. Cerebrospinal fluid SNAP-25 differentiated Alzheimer's disease from controls with area under the curve of 0.901 (P &lt; 0.0001). Conclusions: We developed a sensitive method to analyze SNAP-25 levels in individual CSF samples that to our knowledge was not possible previously. Our results support the notion that synaptic biomarkers may be important tools for early diagnosis, assessment of disease progression, and to monitor drug effects in treatment trials.},
  articleno    = {53},
  author       = {Brinkmalm, Ann and Brinkmalm, Gunnar and Honer, William G. and Frolich, Lutz and Hausner, Lucrezia and Minthon, Lennart and Hansson, Oskar and Wallin, Anders and Zetterberg, Henrik and Blennow, Kaj and Ohrfelt, Annika},
  issn         = {1750-1326},
  keyword      = {Alzheimer's disease,Biomarker,Cerebrospinal fluid,SNAP-25,SNARE,proteins,Mass spectrometry,Immunopurification,Selected reaction,monitoring},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {Molecular Neurodegeneration},
  title        = {SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer's disease},
  url          = {http://dx.doi.org/10.1186/1750-1326-9-53},
  volume       = {9},
  year         = {2014},
}