Ann Brinkmalm (Moelndal / SE), Johanna Nilsson (Moelndal / SE), Elena Camporesi (Moelndal / SE), Juan Lantero Rodriguez (Moelndal / SE), Tammaryn Lashley (London / GB), Henrik Zetterberg (Moelndal / SE), Kaj Blennow (Moelndal / SE), Gunnar Brinkmalm (Moelndal / SE)
Aims:
We have recently developed CSF biomarker panels targeting synaptic dysfunction as well as pathological alterations in the endo-lysosomal and ubiquitin-proteasome systems. Several of the proteins that we have found to be significantly altered in CSF in early stages of AD or PD are synapse-associated membrane-proteins and in some cases, we have identified specific processed protein forms that seem to be disease related. Our aim in this study is to develop a selected reaction monitoring (SRM) mass spectrometry-based panel to characterize and quantify specific forms of synapse associated proteins in brain for possible translation to fluid biomarkers.
Methods:
We have recently developed CSF biomarker panels targeting synaptic dysfunction as well as pathological alterations in the endo-lysosomal and ubiquitin-proteasome systems. Several of the proteins that we have found to be significantly altered in CSF in early stages of AD or PD are synapse-associated membrane-proteins and in some cases, we have identified specific processed protein forms that seem to be disease related. Our aim in this study is to develop a selected reaction monitoring (SRM) mass spectrometry-based panel to characterize and quantify specific forms of synapse associated proteins in brain for possible translation to fluid biomarkers.
Results:
Solid-phase extraction and parallel reaction monitoring mass spectrometry were used to prepare TBS soluble brain homogenate fractions and almost 2000 proteins were identified with low flow liquid chromatography and high-resolution mass spectrometry. High flow liquid chromatography and selected reaction monitoring were used to develop a panel including SNAP-25, syntaxin-1A and B, VAMP2, complexin-1 and 2, SV2A, synaptophysin, and synapsin-1.
Conclusions:
Differential patterns of CSF biomarkers associated to the synapse is probably due to differences in pathology mechanisms. The presented method could be used to compare the biomarkers" diagnostic and disease monitoring potential as well as to investigate specific pathological molecular patterns across and within neurodegenerative diseases.