中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (10): 1719-1730.doi: 10.4103/1673-5374.238608

• 综述:退行性病与再生 • 上一篇    下一篇

区分正常脑老化与阿尔茨海默病的发展:炎症,胰岛素信号传导和认知

  

  • 收稿日期:2018-07-16 出版日期:2018-10-15 发布日期:2018-10-15

Distinguishing normal brain aging from the development of Alzheimer’s disease: inflammation, insulin signaling and cognition

Paul Denver1, 2, Paula L. McClean3   

  1. 1 Greater Los Angeles Veterans Affairs Healthcare System, West Los Angeles Medical Center and Department of Neurology, University of California, Los Angeles, CA, USA
    2 Centre for Molecular Biosciences, University of Ulster, Coleraine, Northern Ireland, UK
    3 Northern Ireland Centre for Stratified Medicine, Clinical, Translational and Research Innovation Centre (C-TRIC), University of Ulster, Derry/Londonderry, Northern Ireland, UK
  • Received:2018-07-16 Online:2018-10-15 Published:2018-10-15
  • Contact: Paul Denver, PhD,pdenver@mednet.ucla.edu
  • Supported by:

    This work was supported by the Department of Education and Learning, Northern Ireland, UK

摘要:

orcid:0000-0003-0712-8341(Paul Denver)

Abstract:

As populations age, prevalence of Alzheimer’s disease (AD) is rising. Over 100 years of research has provided valuable insights into the pathophysiology of the disease, for which age is the principal risk factor. However, in recent years, a multitude of clinical trial failures has led to pharmaceutical corporations becoming more and more unwilling to support drug development in AD. It is possible that dependence on the amyloid cascade hypothesis as a guide for preclinical research and drug discovery is part of the problem. Accumulating evidence suggests that amyloid plaques and tau tangles are evident in non-demented individuals and that reducing or clearing these lesions does not always result in clinical improvement. Normal aging is associated with pathologies and cognitive decline that are similar to those observed in AD, making differentiation of AD-related cognitive decline and neuropathology challenging. In this mini-review, we discuss the difficulties with discerning normal, age-related cognitive decline with that related to AD. We also discuss some neuropathological features of AD and aging, including amyloid and tau pathology, synapse loss, inflammation and insulin signaling in the brain, with a view to highlighting cognitive or neuropathological markers that distinguish AD from normal aging. It is hoped that this review will help to bolster future preclinical research and support the development of clinical tools and therapeutics for AD.

Key words: Alzheimer’s disease, aging, inflammation, cognitive function, spatial learning, insulin signaling, synapses, cytokines