In:
Alzheimer's & Dementia, Wiley, Vol. 16, No. S4 ( 2020-12)
Abstract:
A 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. Method Stable 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.). Result We 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. Conclusion We 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. References: (1) Bagetta, V., et al., Synaptic dysfunction in Parkinson's disease . Biochem Soc Trans, 2010. 38(2): p. 493‐7. (2) Schneider, J.A., et al., The neuropathology of probable Alzheimer disease and mild cognitive impairment . Ann Neurol, 2009. 66(2): p. 200‐8. (3) Schulz‐Schaeffer, W.J., The synaptic pathology of alpha‐synuclein aggregation in dementia with Lewy bodies, Parkinson's disease and Parkinson's disease dementia . Acta Neuropathol, 2010. 120(2): p. 131‐43. (4) Clare, R., et al., Synapse loss in dementias . J Neurosci Res, 2010. 88(10): p. 2083‐90.
Type of Medium:
Online Resource
ISSN:
1552-5260
,
1552-5279
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2201940-6
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