Overview of Proteomic Analysis of Amyloid Plaques and Neurofibrillary Tangles in Alzheimer’s Disease

Abstract

In this review, we describe the methods used for the extraction and mass spectrometry proteomics analysis of amyloid plaques and neurofibrillary tangles (NFTs), the two primary pathological hallmarks of Alzheimer’s disease (AD). We also provide a comprehensive overview of the mass spectrometry-based studies conducted to analyze these pathological features. AD is the most prevalent form of dementia and the sixth leading cause of death in the United States. While the current treatments can alleviate early-stage memory and cognitive symptoms, they do not offer a cure. Thus, there is a pressing need to deepen our understanding of the neuropathological mechanisms underlying AD and to develop more effective therapeutics. In-depth mass spectrometry-based proteomics analyses of AD pathology—specifically, extracellular the Aβ plaques found in extracellular spaces and blood vessel walls and intraneuronal NFTs composed of the microtubule-associated protein tau—may offer molecular-level observations that contribute to the understanding of the biological context of plaque and NFT formation and support the discovery of potential biomarkers and therapeutic targets for AD.