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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\u2014specifically, extracellular the A\u03b2 plaques found in extracellular spaces and blood vessel walls and intraneuronal NFTs composed of the microtubule-associated protein tau\u2014may 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.<\/jats:p>","DOI":"10.3390\/biom15091310","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T15:10:46Z","timestamp":1757603446000},"page":"1310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Overview of Proteomic Analysis of Amyloid Plaques and Neurofibrillary Tangles in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Amber","family":"Grewal","sequence":"first","affiliation":[{"name":"Center for Biomedical Mass Spectrometry, Department of Biochemistry and Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simran","family":"Raikundalia","sequence":"additional","affiliation":[{"name":"Center for Biomedical Mass Spectrometry, Department of Biochemistry and Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9497-8701","authenticated-orcid":false,"given":"Joseph","family":"Zaia","sequence":"additional","affiliation":[{"name":"Center for Biomedical Mass Spectrometry, Department of Biochemistry and Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA"},{"name":"Bioinformatics Program, Boston University, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8276-6728","authenticated-orcid":false,"given":"Manveen K.","family":"Sethi","sequence":"additional","affiliation":[{"name":"Center for Biomedical Mass Spectrometry, Department of Biochemistry and Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1007\/s12264-022-00927-5","article-title":"Focal-type, but not Diffuse-type, Amyloid Beta Plaques are Correlated with Alzheimer\u2019s Neuropathology, Cognitive Dysfunction, and Neuroinflammation in the Human Hippocampus","volume":"38","author":"Liu","year":"2022","journal-title":"Neurosci. 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