Neurofilament light-chain (NfL) in the blood or CSF is a highly predictive biomarker of neuronal dysfunction in multiple diseases. However, NfL in CSF and blood has remained poorly characterized at the protein structure and isoform level. The overall goal of this proposal is to fully characterize NfL isoforms in human AD cerebrospinal fluid and blood with mass spectrometry in order to quantify total and phosphorylated isoforms of NfL, and assess the utility of various NfL isoforms in quantifying AD neurodegeneration. This will aid in identifying disease specific isoforms for future biomarker use, and improve staging AD for asymptomatic and symptomatic individuals and may help discriminate between AD from other neurodegenerative dementias. Towards this goal we will develop and analytically validate a mass spectrometry assay to measure NfL and its isoforms in CSF and blood (aim 1) and compare concentrations and isoforms across samples from individuals with AD, non-AD (FTD, PD, PSP, CBD) and healthy controls (aim 2).
The goal of this project is to develop a mass spectrometry assay to characterize and measure neurofilament light chain (NfL) isoforms, a biomarker of neurodegeneration, in human blood. NfL is elevated in Alzheimer's disease and many other neurodegenerative diseases, and may have a specific signature that could differentiate among neurodegenerative diseases. If successful, this assay would have utility in multiple neurodegenerative diseases including Alzheimer's disease for staging, prognosis, and potentially monitoring therapeutic trials.
