Characterization of Neurofilament Light Chain in Alzheimer's Disease and Other Neurodegenerative Disorders

项目摘要 血液或CSF中的神经丝轻链（NfL）是神经元功能障碍的高度预测性生物标志物， 多种疾病。然而，CSF和血液中的NfL在蛋白质结构方面的特征仍然很差， 异构体水平。该提案的总体目标是充分表征人类AD脑脊液中的NfL亚型 和血液，以定量NfL的总亚型和磷酸化亚型，并评估NfL的表达。 各种NfL同种型在定量AD神经变性中的效用。这将有助于确定疾病的具体 同种型用于未来生物标志物使用，并改善无症状和有症状个体的AD分期， 有助于区分AD和其他神经退行性痴呆。为了实现这一目标，我们将开发和 分析验证质谱法测定CSF和血液中的NfL及其亚型（目的1）， 比较AD和非AD个体样本的浓度和亚型（FTD、PD、PSP、CBD） 和健康对照组（目的2）。

PROJECT SUMMARY 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).