Abstract
AbstractBackgroundA reduction of synaptic activity is one of the earliest events in neurodegenerative diseases such as Alzheimer’s disease (AD)[1‐4]. A 35% loss in the number of synapses have also been found in AD, by using synaptic proteins as markers[3‐4]. Detection and quantification of synaptic markers is therefore a hot topic due to the significant role of synapses in the disease pathology and progression of neurodegenerative diseases. In this study, we developed a novel proteomics assay approach to quantify a panel of 17 synaptic proteins in cerebrospinal fluid. The synaptic panel includes but are not limited to: synucleins, neuronal pentraxins, SNARE proteins and neurogranin.MethodStable isotope labeled peptide standards were added during digestion of 100 µL CSF samples, followed by purification with solid‐phase extraction. Quantification was performed by micro‐high‐performance liquid chromatography (Ultimate 3000 standard liquid chromatography system, Thermo Fisher Scientific Inc,) parallel reaction monitoring mass spectrometry (Q Exactive, Thermo Fisher Scientific Inc.).ResultWe show a novel strategy to quantify 17 synaptic proteins in CSF in parallel to study several properties of synaptic pathology simultaneously. In a CSF pilot study of 20 AD and 20 healthy controls, several synaptic proteins were found to be increased (p‐value≤0.001) such as neurogranin, complexin‐2, VAMP2 and beta‐synuclein. Interestingly, the neuronal pentraxins (NPTX1, NPTX2 and NPTXR) showed no significant difference between AD and control.ConclusionWe have successfully established a method that can measure and compare levels of a panel of synaptic proteins in individual patient CSF samples. The pilot study shows very promising results where several synaptic proteins potentially could be used as biomarkers for synaptic pathology in Alzheimer’s disease.
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