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

作     者：Paul Denver Paula L.McClean 

作者机构：Greater Los Angeles Veterans Affairs Healthcare SystemWest Los Angeles Medical Center and Department of NeurologyUniversity of CaliforniaLos AngelesCAUSA Centre for Molecular BiosciencesUniversity of UlsterColeraine Northern Ireland UK Northern Ireland Centre for Stratified MedicineClinicalTranslational and Research Innovation Centre (C-TRIC)University of UlsterDerry/Londonderry Northern Ireland UK 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2018年第13卷第10期

页      面：1719-1730页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100203[医学-老年医学] 10[医学] 

基　　金：supported by the Department of Education and Learning Northern Ireland UK 

主　　题：Alzheimer's disease aging inflammation cognitive function spatial learning insulin signaling synapses cytokines 

摘      要：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.