Glycoproteins as diagnostic and prognostic biomarkers for neurodegenerative diseases: A glycoproteomic approach

• Published in: Journal of neuroscience research Vol. 99; no. 5; pp. 1308 - 1324
• Main Authors: Xu, Ming‐ming, Zhou, Mao‐tian, Li, Shu‐wei, Zhen, Xue‐chu, Yang, Shuang
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2021
• Subjects: Alzheimer's disease; Amyloid; Biomarkers; Biomarkers - metabolism; Cerebrospinal fluid; Dementia disorders; Diagnostic software; Glycoproteins; Glycoproteins - genetics; Glycoproteins - metabolism; glycoproteomics; Glycosylation; Humans; Mass spectrometry; Mass spectroscopy; Movement disorders; Neurodegeneration; Neurodegenerative diseases; Neurodegenerative Diseases - diagnosis; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - metabolism; Neurons - metabolism; Older people; Parkinson's disease; Pathogenesis; Prognosis; Proteins; Proteomics - methods; Tau protein; glycoproteomics; neurodegenerative diseases; Parkinson's disease; biomarkers; glycosylation; mass spectrometry; Alzheimer's disease
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.24805

Neurodegenerative diseases (NDs) are incurable and can develop progressively debilitating disorders, including dementia and ataxias. Alzheimer's disease and Parkinson's disease are the most common NDs that mainly affect the elderly people. There is an urgent need to develop new diagnostic tools so that patients can be accurately stratified at an early stage. As a common post‐translational modification, protein glycosylation plays a key role in physiological and pathological processes. The abnormal changes in glycosylation are associated with the altered biological pathways in NDs. The pathogenesis‐related proteins, like amyloid‐β and microtubule‐associated protein tau, have altered glycosylation. Importantly, specific glycosylation changes in cerebrospinal fluid, blood and urine are valuable for revealing neurodegeneration in the early stages. This review describes the emerging biomarkers based on glycoproteomics in NDs, highlighting the potential applications of glycoprotein biomarkers in the early detection of diseases, monitoring of the disease progression, and measurement of the therapeutic responses. The mass spectrometry‐based strategies for characterizing glycoprotein biomarkers are also introduced. Neurodegenerative disease (ND) may lead to aberrant changes in glycoenzymes, including glycosyltransferases and glycosidases, which further regulate the key ND‐related molecules, such as amyloid precursor protein, nicastrin, β‐site APP‐cleaving enzyme 1β‐site APP‐cleaving enzyme 1, a disintegrin and metallopeptidase domain 10 (ADAM10), neprilysin, etc.