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Early detection through biomarkers is essential for early intervention. Recent sub\u2010classification of AD through extensive cerebrospinal fluid (CSF) proteomic analyses revealed distinct characteristics of each subtype, necessitating tailored therapeutic strategies. While CSF proteomics has identified potential biomarkers, the need for non\u2010invasive and cost\u2010effective substitutions highlights the importance of blood\u2010based biomarkers (BBMs). This review is a comprehensive review that categorizes potential BBMs based on neuronal hyperplasticity (subtype 1), underlining their role in refining subtype classification and enabling precision medicine. Early AD is often marked by cortical and hippocampal hyperactivity, followed by hypoactivity during later stages of neurodegeneration. While the exact mechanisms remain unclear, factors like Ca\n 2+<\/jats:sup>\n , glutamate, amyloid beta, tau, genetic factors, and impaired glial function play a role. Advancements in blood\u2010based diagnostics would improve detection, individual treatment strategies, and evaluation of therapeutic response, eventually reducing the burden of AD on health\u2010care systems.\n <\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n Alzheimer's disease (AD; subtype 1) exhibits neuronal hyperplasticity, mild cortical atrophy, and moderate microglial activation.<\/jats:p>\n <\/jats:list-item>\n \n The neuronal hyperplasticity subtype of AD is characterized by an upregulation of synaptic and plasticity\u2010related proteins, distinguishing it from other AD subtypes.<\/jats:p>\n <\/jats:list-item>\n \n Identifying biomarkers specific to neuronal hyperplasticity would enable real\u2010time monitoring of therapeutic responses, allowing for individualized therapy as opposed to a \u201cone\u2010size\u2010fits\u2010all\u201d strategy.<\/jats:p>\n <\/jats:list-item>\n \n The treatments based on neuronal hyperactivity reduction, restoration of synaptic plasticity, and anti\u2010inflammation\/metabolic dysfunction would be useful in this AD subtype.<\/jats:p>\n <\/jats:list-item>\n \n Blood\u2010based biomarkers offer a cost\u2010effective and accessible alternative to cerebrospinal fluid and neuroimaging methods.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.70475","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T09:31:37Z","timestamp":1753435897000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Unveiling blood biomarkers for neuronal hyperplasticity: Insights from AD molecular subtyping, a comprehensive review"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6720-257X","authenticated-orcid":false,"given":"Niti","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Bionano Technology Gachon Bionano Research Institute Gachon University Seongnam Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Bionano Technology Gachon Bionano Research Institute Gachon University Seongnam Republic of Korea"},{"name":"Department of Neurology Veterans Medical Research Institute Veterans Health Service Medical Center Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himadri","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Bionano Technology Gachon Bionano Research Institute Gachon University Seongnam Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon Il","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Bionano Technology Gachon Bionano Research Institute Gachon University Seongnam Republic of 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