The Moderating Effect of Serum Vitamin D on the Relationship Between Beta-Amyloid Deposition and Neurodegeneration
Junha Park 1, 2, Min Soo Byun 1, 2, 3*, Dahyun Yi 4, Hyejin Ahn 5, Joon Hyung Jung 6, Nayeong Kong 7, Yoon Young Chang 1, 2, Gijung Jung 4, Jun-Young Lee 1, 8, Yu Kyeong Kim 9, 10, Yun-Sang Lee 10, Koung Mi Kang 11, Chul-Ho Sohn 11, Dong Young Lee 1, 2, 3
1Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea , 2Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea , 3Seoul National University Dementia Research Center, Seoul, Republic of Korea , 4Institute of Human Behavioral Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea, 5Interdisciplinary program of cognitive science, Seoul National University College of Humanities, Seoul, Republic of Korea, 6Department of Psychiatry, Chungbuk National University Hospital, Cheongju, Republic of Korea, 7Department of Psychiatry, Keimyung University Dongsan Medical Center, Daegu, Republic of Korea, 8Department of Neuropsychiatry, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea, 9Department of Nuclear Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea, 10Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea , 11Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Republic of Korea
Received: March 16, 2024; Revised: June 1, 2024; Accepted: June 9, 2024; Published online: June 9, 2024.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
Objective: Previous studies have reported that vitamin D deficiency increased the risk of Alzheimer’s disease (AD) dementia in older adults. However, little is known about how vitamin D is involved in the pathophysiology of AD. Thus, this study aimed to examine the association and interaction of serum vitamin D levels with in vivo AD pathologies including cerebral beta-amyloid (Aβ) deposition and neurodegeneration in nondemented older adults.
Methods: 428 nondemented older adults were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease, a prospective cohort that began in 2014. All participants underwent comprehensive clinical assessments, measurement of serum 25-hydroxyvitamin D (25[OH]D), and multimodal brain imaging including Pittsburgh compound-B (PiB) positron emission tomography and magnetic resonance imaging. Global PiB deposition was measured for the Aβ biomarker. Intracranial volume-adjusted hippocampal volume (HVa) was used as a neurodegeneration biomarker.
Results: Overall, serum 25(OH)D level was not associated with either Aβ deposition or HVa after controlling for age, sex, apolipoprotein E ε4 positivity, and vascular risk factors. However, serum 25(OH)D level had a significant moderation effect on the association between Aβ and neurodegeneration, with lower serum 25(OH)D level significantly exacerbating cerebral Aβ-associated hippocampal volume loss (β = 34.612, p = 0.008).
Discussion: Our findings indicate that lower serum vitamin D levels may contribute to AD by exacerbating Aβ-associated neurodegeneration in nondemented older adults. Further studies to explore the potential therapeutic effect of vitamin D supplementation on the progression of AD pathology will be necessary.
Keywords: Alzheimer, Vitamin D, Beta-amyloid, Neurodegeneration, Moderation effect, Biomarker


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