title: SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer's disease.
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 < 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.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden. ann.brinkmalm@neuro.gu.se.
authors.forename: Ann
authors.initials: A
authors.lastname: Brinkmalm
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brinkmalm
authors.forename: William G
authors.initials: WG
authors.lastname: Honer
authors.forename: Lutz
authors.initials: L
authors.lastname: Frölich
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Hausner
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
authors.forename: Anders
authors.initials: A
authors.lastname: Wallin
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Annika
authors.initials: A
authors.lastname: Öhrfelt
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology; D019540:Area Under Curve; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000134:cerebrospinal fluid*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013569:Synapses / Q000473:pathology*; D050825:Synaptosomal-Associated Protein 25 / Q000134:cerebrospinal fluid*; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25