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

被引:221
作者
Brinkmalm, Ann [1 ]
Brinkmalm, Gunnar [1 ]
Honer, William G. [2 ]
Frolich, Lutz [3 ]
Hausner, Lucrezia [3 ]
Minthon, Lennart [4 ,5 ]
Hansson, Oskar [4 ,5 ]
Wallin, Anders [1 ]
Zetterberg, Henrik [1 ,6 ]
Blennow, Kaj [1 ]
Ohrfelt, Annika [1 ]
机构
[1] Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, S-43180 Molndal, Sweden
[2] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada
[3] Heidelberg Univ, Cent Inst Mental Hlth Mannheim, Dept Geriatr Psychiat, Mannheim, Germany
[4] Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Lund, Sweden
[5] Skane Univ Hosp, Mem Clin, Skane, Sweden
[6] UCL Inst Neurol, London WC1N 3BG, England
基金
加拿大健康研究院; 瑞典研究理事会;
关键词
Alzheimer's disease; Biomarker; Cerebrospinal fluid; SNAP-25; SNARE proteins; Mass spectrometry; Immunopurification; Selected reaction monitoring; SYNAPTOSOMAL-ASSOCIATED PROTEIN; PRESYNAPTIC PROTEINS; MEMBRANE-FUSION; AMYLOID-BETA; PATHOLOGY; IDENTIFICATION; DEMENTIA; VESICLE; CORTEX; SNARE;
D O I
10.1186/1750-1326-9-53
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
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页数:13
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