Unveiling blood biomarkers for neuronal hyperplasticity: Insights from AD molecular subtyping, a comprehensive review.
| Title: | Unveiling blood biomarkers for neuronal hyperplasticity: Insights from AD molecular subtyping, a comprehensive review. |
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| Authors: | Sharma N; Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, Seongnam, Republic of Korea.; Kim D; Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, Seongnam, Republic of Korea.; Department of Neurology, Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Republic of Korea.; Sharma H; Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, Seongnam, Republic of Korea.; Kim MI; Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, Seongnam, Republic of Korea.; Lee H; Department of Neurology, Gachon University Gil Hospital, Incheon, Republic of Korea.; Kim M; Department of Neurology, Seoul National University College of Medicine & Seoul National University Bundang Hospital, Seongnam, Republic of Korea.; Ryoo N; Department of Neurology, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.; Kang MJ; Department of Neurology, Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Republic of Korea.; Pyun JM; Department of Neurology, Seoul National University College of Medicine & Seoul National University Bundang Hospital, Seongnam, Republic of Korea.; Park YH; Department of Research and Development, PeopleBio Inc, Seongnam, Republic of Korea.; Ryu J; Department of Research and Development, PeopleBio Inc, Seongnam, Republic of Korea.; Oh HJ; Department of Research and Development, PeopleBio Inc, Seongnam, Republic of Korea.; Yang HS; Department of Neurology, Brigham and Women's Hospital/Harvard Medical School, Boston, USA.; Kim HR; Department of Neurology, Dongguk University Ilsan Hospital, Goyang, Republic of Korea.; Kim GH; Department of Neurology, Ewha Woman's University Mokdong Hospital, Ewha Woman's University College of Medicine, Seoul, Republic of Korea.; Han S; Department of Neurology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.; Yang Y; Department of Neurology, Soonchunhyang University Hospital, Cheonan, Republic of Korea.; Youn YC; Department of Neurology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.; Teunissen C; Neurochemistry Laboratory, Department of Clinical Chemistry, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.; Zetterberg H; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.; UK Dementia Research Institute at UCL, London, UK.; Hong Kong Center for Neurodegenerative Diseases, Science Park, Hong Kong.; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison, Health Sciences Learning Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.; Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Scheltens P; Department of Neurology & Alzheimer Center, Amsterdam University Medical Center, Amsterdam, Netherlands.; An SSA; Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, Seongnam, Republic of Korea.; Kim YB; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, USA.; Kim S; Department of Neurology, Seoul National University College of Medicine & Seoul National University Bundang Hospital, Seongnam, Republic of Korea. |
| Corporate Authors: | Alzheimer's Disease All Markers (ADAM) Research Group |
| Source: | Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2025 Jul; Vol. 21 (7), pp. e70475. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: John Wiley & Sons, Ltd Country of Publication: United States NLM ID: 101231978 Publication Model: Print Cited Medium: Internet ISSN: 1552-5279 (Electronic) Linking ISSN: 15525260 NLM ISO Abbreviation: Alzheimers Dement Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2020- : Hoboken, NJ : John Wiley & Sons, Ltd.; Original Publication: Orlando, FL : Elsevier, Inc. |
| MeSH Terms: | Biomarkers*/blood ; Alzheimer Disease*/blood ; Alzheimer Disease*/pathology ; Alzheimer Disease*/classification ; Alzheimer Disease*/diagnosis ; Neurons*/pathology; Humans |
| Abstract: | Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, predominantly affecting the aging population. Early detection through biomarkers is essential for early intervention. Recent sub-classification 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-invasive and cost-effective substitutions highlights the importance of blood-based 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 Ca2+, glutamate, amyloid beta, tau, genetic factors, and impaired glial function play a role. Advancements in blood-based diagnostics would improve detection, individual treatment strategies, and evaluation of therapeutic response, eventually reducing the burden of AD on health-care systems. HIGHLIGHTS: Alzheimer's disease (AD; subtype 1) exhibits neuronal hyperplasticity, mild cortical atrophy, and moderate microglial activation. The neuronal hyperplasticity subtype of AD is characterized by an upregulation of synaptic and plasticity-related proteins, distinguishing it from other AD subtypes. Identifying biomarkers specific to neuronal hyperplasticity would enable real-time monitoring of therapeutic responses, allowing for individualized therapy as opposed to a "one-size-fits-all" strategy. The treatments based on neuronal hyperactivity reduction, restoration of synaptic plasticity, and anti-inflammation/metabolic dysfunction would be useful in this AD subtype. Blood-based biomarkers offer a cost-effective and accessible alternative to cerebrospinal fluid and neuroimaging methods.; (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.) |
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| Grant Information: | RS-2023-00251396 National Research Foundation of Korea; RS-2021-NR060117 Ministry of Education; 2021R1A6A1A03038996 Ministry of Education; RS-2025-02292973 Korea Institute of Marine Science & Technology Promotion (KIMST) |
| Contributed Indexing: | Keywords: Alzheimer's disease; blood biomarkers; neuronal hyperplasticity; personalized treatment |
| Substance Nomenclature: | 0 (Biomarkers) |
| Entry Date(s): | Date Created: 20250725 Date Completed: 20250725 Latest Revision: 20260519 |
| Update Code: | 20260520 |
| PubMed Central ID: | PMC12290491 |
| DOI: | 10.1002/alz.70475 |
| PMID: | 40709526 |
| Database: | MEDLINE |
Journal Article; Review