Recent Advances in Mass Spectrometry-Based Studies of Post-Translational Modifications in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline. There are more than 10 million new cases of AD each year worldwide, implying one new case every 3.2 s. Post-translational modifications (PTMs) such as phosphorylation, glycosylation, and citrullination have emerged as key modulators of protein function in AD, influencing protein aggregation, clearance, and toxicity. Mass spectrometry (MS) has become an indispensable tool for detecting and quantifying these PTMs, offering valuable insights into their role in AD pathogenesis. This review explores recent advancements in MS-based studies of PTMs in AD, with emphasis on MS techniques, such as data-dependent acquisition (DDA) and data-independent acquisition (DIA), as well as enrichment methods used to characterize PTMs. The applications of these MS-based approaches to the study of various PTMs are highlighted, which have significantly accelerated the biomarker discovery process, providing new avenues for early diagnosis and therapeutic targeting. Advances in biological understanding and analytical techniques, while addressing the challenges and future directions, will be discussed.