Scholarlink

<p>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 <i>Apom</i><sup>-/-</sup> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

HDL-bound S1P affects the subventricular niche and early neuropathological features of Alzheimer’s disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月1日

查看全文
  • Byung Jo Choi,
  • Ju Yeon Hong,
  • Min Hee Park,
  • Kang Ho Park,
  • Wan Hui Han,
  • Hee Ji Yoon,
  • Hye Yoon Jung,
  • Kyung Yeol Kim,
  • Sun Ae Lee,
  • Eun Young Lim,
  • Jung Woo Hur,
  • Im-Sook Song,
  • So Yeon Jeon,
  • Min-Koo Choi,
  • Christina Christoffersen,
  • Hee-Jin Kim,
  • Seung Hyun Kim,
  • Edward H. Schuchman,
  • Jae-sung Bae,
  • Hee Kyung Jin

摘要

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.