Scholarlink

<p>Alzheimer’s disease (AD) is presented as multiple clinical variants depending upon the rate of progression and familial background; however, the exact molecular mechanisms associated with these subtypes and their treatments are yet to be understood. The current study is based on a global proteome analysis of brain samples from patients (<i>n</i> = 38) with rapidly progressive AD (rpAD—survival time &lt; 3&#xa0;years), sporadic AD (spAD—survival time of 8–10&#xa0;years), and healthy controls. Proteome analysis revealed a differential regulation of 79 proteins and highlighted the dysregulation of mitochondrial machinery and glucose metabolism in rpAD. Dihydrolipoamide dehydrogenase (DLDH), a mitochondrial oxidoreductase, showed a significant reduction and delocalization in rpAD. In vitro analysis revealed a potential role of DLDH in the aggregation of amyloid beta. Rapid progression in AD may be influenced by the energy homeostasis and redox dysfunction linked with the DLDH.</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

Proteomic Profiling Reveals Mitochondrial Dysregulation in Rapidly Progressive Alzheimer’s: Role of DLDH in Amyloid Beta Aggregation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月19日

查看全文
  • Saima Zafar,
  • Aneeqa Noor,
  • Neelam Younas,
  • Mohsin Shafiq,
  • Kathrin Dittmar,
  • Oleksandr Yagensky,
  • Matthias Schmitz,
  • Isidre Ferrer,
  • Peter Hermann,
  • Inga Zerr

摘要

Alzheimer’s disease (AD) is presented as multiple clinical variants depending upon the rate of progression and familial background; however, the exact molecular mechanisms associated with these subtypes and their treatments are yet to be understood. The current study is based on a global proteome analysis of brain samples from patients (n = 38) with rapidly progressive AD (rpAD—survival time < 3 years), sporadic AD (spAD—survival time of 8–10 years), and healthy controls. Proteome analysis revealed a differential regulation of 79 proteins and highlighted the dysregulation of mitochondrial machinery and glucose metabolism in rpAD. Dihydrolipoamide dehydrogenase (DLDH), a mitochondrial oxidoreductase, showed a significant reduction and delocalization in rpAD. In vitro analysis revealed a potential role of DLDH in the aggregation of amyloid beta. Rapid progression in AD may be influenced by the energy homeostasis and redox dysfunction linked with the DLDH.