진희경 (경북대학교 수의과대학) | 한빛사논문 > 한빛사

한빛사논문

조회170

경북대학교 수의과대학

CV File

Nat. Commun., Jul 01 2025, 16 (1) | https://doi.org/10.1038/s41467-025-60750-0 HDL-bound S1P affects the subventricular niche and early neuropathological features of Alzheimer's disease

Byung Jo Choi^1,2, Ju Yeon Hong^1,2, Min Hee Park^1,2, Kang Ho Park^1,2, Wan Hui Han^1,2, Hee Ji Yoon^1,2, Hye Yoon Jung^1,2, Kyung Yeol Kim^1,2, Sun Ae Lee^1,2, Eun Young Lim^1,2, Jung Woo Hur^1,2, Im-Sook Song³, So Yeon Jeon⁴, Min-Koo Choi⁴, Christina Christoffersen^5,6, Hee-Jin Kim⁷, Seung Hyun Kim⁷, Edward H. Schuchman⁸, Jae-sung Bae^1,2 & Hee Kyung Jin^1,9

¹KNU AD Research Institute, Kyungpook National University, Daegu, South Korea.
²Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, South Korea.
³BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, Vessel-Organ Interaction Research Center (VOICE), College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, South Korea.
⁴College of Pharmacy, Dankook University, Cheon-an, South Korea.
⁵Department of Clinical Biochemistry, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark.
⁶Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3A, Copenhagen, Denmark.
⁷Department of Neurology, College of Medicine, Hanyang University, Seoul, South Korea.
⁸Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁹Department of Laboratory Animal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu, South Korea.

Corresponding authors
Correspondence to Jae-sung Bae or Hee Kyung Jin.

Abstract

Circulating blood factors are critical for homeostasis of the adult ventricular-subventricular (V-SVZ) and subgranular zones, which contain neural stem cells (NSCs) crucial for sustained neurogenesis. Circulating sphingosine-1-phosphate (S1P) bound to apolipoprotein M (ApoM), a principal component of high-density lipoproteins, is involved in various biological processes, but its role in neurogenic niches is poorly understood. Herein, using Apom^-/- mice, we show that blood ApoM-S1P deficiency impairs the SVZ-NSC pool, neurogenesis, ependymal cell polarity, and cerebrospinal fluid flow, leading to olfactory dysfunction and ventricular enlargement, early neuropathological features of Alzheimer's disease (AD). Enhancing the complex significantly rescues these defects by activating S1P1 receptor signaling in SVZ-NSCs. Consistently, blood ApoM-S1P levels are reduced in early AD patients and correlate with olfactory deficits and ventricular enlargement. Similar abnormalities are recapitulated in young APP/PS1 mice and reversed by restoring blood ApoM-S1P levels. Thus, these data reveal pathogenic mechanisms underlying early neuropathological features of AD and identify the blood ApoM-S1P complex as a potential diagnostic and therapeutic target.

논문정보