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Amelioration of Alzheimer's disease pathology and cognitive deficits by immunomodulatory agents in animal models of Alzheimer's disease

查看全文 作　　者：Bridget [1,2,3]Martinez;Philip [4]V.Peplow 高影响力作者 机构地区：[1]Department of Molecular & Cellular Biology,University of California;[2]Department of Medicine,St.Georges University School of Medicine;[3]Department of Physics and Engineering,Los Alamos National Laboratory;[4]Department of Anatomy,University of Otago高影响力机构 出　　处：《Neural Regeneration Research》索引2019年第14卷第7期,共19页高影响力期刊 摘　　要：The most common age-related neurodegenerative disease is Alzheimer's disease(AD) characterized by aggregated amyloid-β(Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles,together with loss of cholinergic neurons,synaptic alterations,and chronic inflammation within the brain.These lead to progressive impairment of cognitive function.There is evidence of innate immune activation in AD with microgliosis.Classically-activated microglia(M1 state) secrete inflammatory and neurotoxic mediators,and peripheral immune cells are recruited to inflammation sites in the brain.The few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable effects.Translation of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical trials.Treatment with immunomodulatory/anti-inflammatory agents early in the disease process,while not preventive,is able to inhibit the inflammatory consequences of both Aβ and tau aggregation.The studies described in this review have identified several agents with immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of AD.The majority of the animal studies reviewed had used transgenic models of early-onset AD.More effort needs to be given to creat models of late-onset AD.The effects of a combinational therapy involving two or more of the tested pharmaceutical agents,or one of these agents given in conjunction with one of the cell-based therapies,in an aged animal model of AD would warrant investigation. 关 键 词：Alzheimer’s disease NEUROPATHOLOGY cognitive deficits behavioral deficits IMMUNOMODULATORY agents animal models AMYLOID deposits GLIOSIS
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