Bridging the barrier: insights into blood biomarkers and therapeutic strategies targeting choroid plexus and BBB dysfunction in alzheimer's disease.
| Title: | Bridging the barrier: insights into blood biomarkers and therapeutic strategies targeting choroid plexus and BBB dysfunction in alzheimer's disease. |
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| Authors: | Sharma N; Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, 13120, Republic of Korea.; Kim D; Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, 13120, Republic of Korea.; Department of Neurology, Veterans Medical Research Institute, Veterans Health Service Medical Center, 53, Jinhwang-ro 61-gil, Gangdong-gu, Seoul, 05368, Republic of Korea.; Sharma H; Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, 13120, Republic of Korea.; Kim MI; Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, 13120, Republic of Korea.; Lee H; Department of Neurology, Gachon University Gil Hospital, 21, Namdong-daero 774Beon-gil, Namdong-gu, Incheon, 21565, Republic of Korea.; Kim M; Department of Neurology, Seoul National University College of Medicine & Seoul National University Bundang Hospital, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.; Ryoo N; Department of Neurology, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, 1021, Tongil-ro, Eunpyeong-gu, Seoul, Republic of Korea.; Kang MJ; Department of Neurology, Veterans Medical Research Institute, Veterans Health Service Medical Center, 53, Jinhwang-ro 61-gil, Gangdong-gu, Seoul, 05368, Republic of Korea.; Pyun JM; Department of Neurology, Seoul National University College of Medicine & Seoul National University Bundang Hospital, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.; Park YH; Department of Neurology, Seoul National University College of Medicine & Seoul National University Bundang Hospital, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.; Ryu J; Department of Research and Development, PeopleBio Inc., 242 Pangyo-ro, 6fl. PDC C-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, 13487, Republic of Korea.; Oh HJ; Department of Research and Development, PeopleBio Inc., 242 Pangyo-ro, 6fl. PDC C-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, 13487, Republic of Korea.; Yang HS; Department of Neurology, Brigham and Women's Hospital/Harvard Medical School, 60 Fenwood Rd 1 Floor, Boston, MA, 02115, USA.; Kim HR; Department of Neurology, Dongguk University Ilsan Hospital, 27 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea.; Kim GH; Department of Neurology, Ewha Woman's University Mokdong Hospital, Ewha Woman's University College of Medicine, 1071, Anyangcheon-ro, Yangcheon-gu, Seoul, 07985, Republic of Korea.; Han S; Department of Neurology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, 04401, Republic of Korea.; Yang Y; Department of Neurology, Soonchunhyang University Hospital, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan-si, Chungcheongnam-do, 31538, Republic of Korea.; Youn YC; Department of Neurology, Chung-Ang University College of Medicine, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, Republic of Korea.; Teunissen C; Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1105, Amsterdam, 1081 HV, Netherlands.; Zetterberg H; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, 43180, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, 43139, Sweden.; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.; Dementia Research Institute at UCL, Unit 3a, 338 Euston Rd., London, NW1 3BT, UK.; Kong Center for Neurodegenerative Diseases, Units 1501-1502, 1512-1518, 15/F Building 17W, 17 Science Park W Ave, Science Park, Hong Kong, Hong Kong.; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Health Sciences Learning Center, 750 Highland Ave, Madison, WI, 53726, USA.; Scheltens P; Department of Neurology & Alzheimer Center, Amsterdam University Medical Center, Meibergdreef 9, Amsterdam, 1105 AZ, Netherlands.; An SSA; Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, 13120, Republic of Korea. seongaan@gachon.ac.kr.; Kim YB; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA.; Kim S; Department of Neurology, Seoul National University College of Medicine & Seoul National University Bundang Hospital, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea. neuroksy@snu.ac.kr. |
| Corporate Authors: | Alzheimer’s Disease All Markers (ADAM) Research Group |
| Source: | Biomarker research [Biomark Res] 2025 Sep 26; Vol. 13 (1), pp. 116. Date of Electronic Publication: 2025 Sep 26. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: BioMed Central Country of Publication: England NLM ID: 101607860 Publication Model: Electronic Cited Medium: Print ISSN: 2050-7771 (Print) Linking ISSN: 20507771 NLM ISO Abbreviation: Biomark Res Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: London : BioMed Central, 2013- |
| Abstract: | Alzheimer's disease (AD) is the most common cause of dementia and accounts for approximately 60-80% of total dementia patients. Currently, accurate diagnosis for AD relies on cerebrospinal fluid (CSF) sampling or a positron emission tomography (PET) scan, methods that cannot be done in primary care centers where most people go with cognitive complaints. This Limitation calls for the urgent need to develop blood-related diagnostic tests that could facilitate early detection and enable timely treatment. Recent CSF proteomic research categorized AD into five molecular subtypes with discrete Genetic risk profiles. Subtypes 1-3, namely neuronal hyperplasticity, innate immune activation, and RNA dysregulation, were characterized by more classical AD-related changes, like accumulation of amyloid/tau and synaptic and immune dysfunction, respectively. On the contrary, non-traditional AD mechanisms in subtypes 4-5 were choroid plexus (CP) dysfunction and blood-brain barrier (BBB) dysfunction, emphasizing clearance deficits in association with brain barrier dysfunction. The unchanged tau levels later may be explained by an alternate disease mechanism (clearance dysfunction). These subtypes included BBB and CP dysfunction. Biomarker identification based on the mechanism of disease progression would increase the precision of diagnoses, allowing for tailored interventions and aiding in the creation of novel therapies for subtypes that might not react favorably to conventional amyloid/tau-targeting strategies. Finding biomarkers specific to each subtype would aid in patient classification, resulting in more individualized therapy as opposed to a "one-size-fits-all" strategy. The present review emphasized the importance of identifying blood-based biomarkers (BBMs) related to brain barrier dysfunction from CSF studies and personalized treatment strategies to streamline the diagnostic workup, and may be utilized in standard clinical practice for the early detection of AD.; (© 2025. The Author(s).) |
| Competing Interests: | Declarations. Ethics and Consent to Participate Declarations: Not applicable. Consent to Participate declaration: Not applicable. Competing interests: HZ serves at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche, and was a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which was a part of the GU Ventures Incubator Program (outside submitted work). The rest of the authors have nothing to declare. |
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| Grant Information: | RS-2023-00251396 National Research Foundation of Korea (NRF); RS-2025-02292973 Korea Institute of Marine Science and Technology promotion |
| Contributed Indexing: | Keywords: Alzheimer’s disease; BBB dysfunction; Blood Biomarkers; Choroid Plexus dysfunction; Early detection; Personalized treatment |
| Entry Date(s): | Date Created: 20250927 Date Completed: 20250927 Latest Revision: 20250930 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12465532 |
| DOI: | 10.1186/s40364-025-00829-4 |
| PMID: | 41013670 |
| Database: | MEDLINE |
Journal Article; Review