Analyzing the glial proteome in Alzheimer’s disease

ABSTRACTIntroduction Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, memory loss, and changes in behavior. Accumulating evidence indicates that dysfunction of glial cells, including astrocytes, microglia, and oligodendrocytes, may contribute to the development and progression of AD. Large-scale analysis of glial proteins sheds light on their roles in cellular processes and diseases. In AD, glial proteomics has been utilized to understand glia-based pathophysiology and identify potential biomarkers and therapeutic targets.Area covered In this review, we provide an updated overview of proteomic analysis of glia in the context of AD. Additionally, we discuss current challenges in the field, involving glial complexity and heterogeneity, and describe some cutting-edge proteomic technologies to address them.Expert opinion Unbiased comprehensive analysis of glial proteomes aids our understanding of the molecular and cellular mechanisms of AD pathogenesis. These investigations highlight the crucial role of glial cells and provide novel insights into the mechanisms of AD pathology. A deeper understanding of the AD-related glial proteome could offer a repertoire of potential biomarkers and therapeutics. Further technical advancement of glial proteomics will enable us to identify proteins within individual cells and specific cell types, thus significantly enhancing our comprehension of AD pathogenesis.KEYWORDS: Alzheimer's diseasebiomarkergliaproteomeproteomics Article highlights Glial cells in Alzheimer's disease (AD) undergo profound molecular and functional alterations, offering vast possibilities for biomarker identification and therapeutic breakthroughs.Technological advancements in the proteomic field have facilitated the identification of distinct proteomic changes specific to individual glial cell types in AD.Identifying and characterizing the glia-specific proteomic alterations in AD holds potential for both disease diagnosis and treatment.Further refinement of highly sensitive proteomic techniques is imperative to unlock glia-based biomarkers that can enable timely diagnosis and treatment of AD.Declaration of interestsThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royaltiesReviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.AcknowledgmentsAll authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. J-HK, RA, and KS formulated the focus of this review. RA and W-HL conducted the literature review and participated in the discussion. J-HK and KS wrote the manuscript. W-HL and KS revised and critically reviewed.Additional informationFundingThis work was supported by the Basic Science Research Program through the National Research Foundation (NRF), which is funded by the Korean government (MSIP) (NRF-2017R1A5A2015391, 2020M3E5D9079764).