Niti Sharma (가천대학교) | 한빛사논문 > 한빛사

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Alzheimers. Dement., Jul 2025, 21 (7) | https://doi.org/10.1002/alz.70475 Unveiling blood biomarkers for neuronal hyperplasticity: Insights from AD molecular subtyping, a comprehensive review

Niti Sharma¹, Danyeong Kim ^{1 2}, Himadri Sharma ¹, Moon Il Kim ¹, Hyon Lee ³, Minju Kim ⁴, Nayoung Ryoo ⁵, Min Ju Kang ², Jung-Min Pyun ⁴, Young Ho Park ⁶, Jisun Ryu ⁶, Hyun Jung Oh ⁶, Hyun-Sik Yang ⁷, Hang-Rai Kim ⁸, Geon Ha Kim ⁹, Sangwon Han ¹⁰, YoungSoon Yang ¹¹, Young Chul Youn ¹², Charlotte Teunissen ¹³, Henrik Zetterberg^{14 15 16 17 18 19}, Philip Scheltens²⁰, Seong Soo A. An ^{1 *}, Young-Bum Kim ²¹, SangYun Kim^{4 *} ; Alzheimer's Disease All Markers (ADAM) Research Group

¹Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, Seongnam, Republic of Korea.
²Department of Neurology, Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Republic of Korea.
³Department of Neurology, Gachon University Gil Hospital, Incheon, Republic of Korea.
⁴Department of Neurology, Seoul National University College of Medicine & Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
⁵Department of Neurology, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
⁶Department of Research and Development, PeopleBio Inc, Seongnam, Republic of Korea.
⁷Department of Neurology, Brigham and Women's Hospital/Harvard Medical School, Boston, USA.
⁸Department of Neurology, Dongguk University Ilsan Hospital, Goyang, Republic of Korea.
⁹Department of Neurology, Ewha Woman's University Mokdong Hospital, Ewha Woman's University College of Medicine, Seoul, Republic of Korea.
¹⁰Department of Neurology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.
¹¹Department of Neurology, Soonchunhyang University Hospital, Cheonan, Republic of Korea.
¹²Department of Neurology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
¹³Neurochemistry Laboratory, Department of Clinical Chemistry, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
¹⁴Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁵Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
¹⁶UK Dementia Research Institute at UCL, London, UK.
¹⁷Hong Kong Center for Neurodegenerative Diseases, Science Park, Hong Kong.
¹⁸Wisconsin 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.
¹⁹Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
²⁰Department of Neurology & Alzheimer Center, Amsterdam University Medical Center, Amsterdam, Netherlands.
²¹Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, USA.

^*Corresponding authors: correspondence to Seong Soo A. An or SangYun Kim

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.

논문정보

형식Review Paper
게재일2025년 07월 (BRIC 등록일 2025-07-28)
연구진국내(교신)+국외 연구진
분야 의약학 > 신경의학

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