Using stable isotope labeling to advance our understanding of Alzheimer’s disease etiology and pathology

Abstract

Stable isotope labeling with mass spectrometry (MS)‐based proteomic analysis has become a powerful strategy to assess protein steady‐state levels, protein turnover, and protein localization. Applying these analyses platforms to neurodegenerative disorders may uncover new aspects of the etiology of these devastating diseases. Recently, stable isotopes‐MS has been used to investigate early pathological mechanisms of Alzheimer s disease (AD) with mouse models of AD‐like pathology. In this review, we summarize these stable isotope‐MS experimental designs and the recent application in the context of AD pathology. We also describe our current efforts aimed at using nuclear magnetic resonance (NMR) analysis of stable isotope‐labeled amyloid fibrils from AD mouse model brains. Collectively, these methodologies offer new opportunities to study proteome changes in AD and other neurodegenerative diseases by elucidating mechanisms to target for treatment and prevention.