The Moderating Effect of Serum Vitamin D on the Relationship between Beta-amyloid Deposition and Neurodegeneration
Junha Park1,2, Min Soo Byun1,2,3, Dahyun Yi4, Hyejin Ahn5, Joon Hyung Jung1,6, Nayeong Kong7, Yoon Young Chang1,8, Gijung Jung4, Jun-Young Lee1,9, Yu Kyeong Kim10,11, Yun-Sang Lee11, Koung Mi Kang12, Chul-Ho Sohn12, Dong Young Lee1,2,3,4,5; for the KBASE Research Group
1Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea
2Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Korea
3Convergence Research Center for Dementia, Seoul National University Medical Research Center, Seoul, Korea
4Institute of Human Behavioral Medicine, Seoul National University Medical Research Center, Seoul, Korea
5Interdisciplinary Program of Cognitive Science, College of Humanities, Seoul National University, Seoul, Korea
6Department of Psychiatry, Chungbuk National University Hospital, Cheongju, Korea
7Department of Psychiatry, Keimyung University Dongsan Medical Center, Daegu, Korea
8Department of Psychiatry, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
9Department of Neuropsychiatry, SMG-SNU Boramae Medical Center, Seoul, Korea
10Department of Nuclear Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea
11Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea
12Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea
Correspondence to: Min Soo Byun
Department of Psychiatry, Seoul National University College of Medicine & Seoul National University Hospital, 101 Daehak-ro, Jongro-gu, Seoul 03080, Korea
E-mail: byunms@snu.ac.kr
ORCID: https://orcid.org/0000-0003-3159-4510
Received: March 22, 2024; Revised: June 1, 2024; Accepted: June 9, 2024; Published online: July 25, 2024.
© The Korean College of Neuropsychopharmacology. All rights reserved.

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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 ɛ4 positivity, and vascular risk factors. However, serum 25(OH)D level had a significant moderating effect on the association between Aβ and neurodegeneration, with lower serum 25(OH)D level significantly exacerbating cerebral Aβ-associated hippocampal volume loss (B = 34.612, p = 0.008).
Conclusion: 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 disease; Vitamin D; Neuroimaging; Biomarkers

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