中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (2): 685-686.doi: 10.4103/NRR.NRR-D-24-01006

• 观点:退行性病与再生 • 上一篇    下一篇

抑制mTOR预防阿尔茨海默病:针对APOE4携带者的代谢和血管恢复

  

  • 出版日期:2026-02-15 发布日期:2025-05-23

Rapamycin as a preventive intervention for Alzheimer’s disease in APOE4 carriers: Targeting brain metabolic and vascular restoration

Ai-Ling Lin* , Chetan Aware   

  1. Department of Radiology, University of Missouri, Columbia, MO, USA (Lin AL, Aware C) NextGen Precision Health, University of Missouri, Columbia, MO, USA (Lin AL, Aware C) Division of Biological Sciences, University of Missouri, Columbia, MO, USA (Lin AL) Institute for Data Science and Informatics, University of Missouri, Columbia, MO, USA (Lin AL)
  • Online:2026-02-15 Published:2025-05-23
  • Contact: Ai-Ling Lin, PhD, ai-ling.lin@health.missouri.edu.
  • Supported by:
    This work was supported by National Institute on Aging (NIH-NIA) R01AG054459 (to ALL).

摘要: https://orcid.org/0000-0002-5197-2219 (Ai-Ling Lin)

Abstract: Alzheimer ’s disease (AD) is the most common form of dementia, affecting over 50 million people worldwide. This figure is projected to nearly double every 20 years, reaching 82 million by 2030 and 152 million by 2050 (Alzheimer’s Disease International). The apolipoprotein ε4 (APOE4) allele is the strongest genetic risk factor for late-onset AD (after age 65 years). Apolipoprotein E, a lipid transporter, exists in three variants: ε2, ε3, and ε4. APOE ε2 (APOE2) is protective against AD, APOE ε3 (APOE3) is neutral, while APOE4 significantly increases the risk. Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD, and those with two copies face an 8-fold risk compared to non-carriers. Even in cognitively normal individuals, APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta (Aβ) plaques and neurofibrillary tau tangles emerge—the hallmark pathologies of AD (Reiman et al., 2001, 2005; Thambisetty et al., 2010). Notably, studies have demonstrated reduced glucose uptake, or hypometabolism, in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers, long before clinical symptoms arise (Reiman et al., 2001, 2005).