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

Martinez, Bridget; Peplow, Ph.D., Philip V

doi:10.4103/1673-5374.251192

Title: Amelioration of Alzheimer’s disease pathology and cognitive deficits by immunomodulatory agents in animal models of Alzheimer’s disease

Journal Article · Tue Jan 01 00:00:00 EST 2019 · Neural Regeneration Research

DOI:https://doi.org/10.4103/1673-5374.251192· OSTI ID:1628700

Martinez, Bridget ^[1]; Peplow, Ph.D., Philip V ^[2]

Univ. of California, Merced, Merced, CA (United States). Dept. of Molecular & Cellular Biology; St. Georges Univ. School of Medicine, Grenada. Dept. of Medicine; Los Alamos National Lab (LANL), Los Alamos, NM (United States). Dept. of Physics and Engineering
Univ. of Otago, Dunedin, New Zealand. Dept. of Anatomy

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 create 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.

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Research Organization:: Los Alamos National Lab (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC52-06NA25396

OSTI ID:: 1628700

Journal Information:: Neural Regeneration Research, Vol. 14, Issue 7; ISSN 1673-5374

Publisher:: Chinese Association of Rehabilitation Medicine (CARM)Copyright Statement

Country of Publication:: United States

Language:: English

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