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Drugs Fut 2017, 42(1): 21
ISSN 0377-8282
Copyright 2017 Clarivate Analytics
CCC: 0377-8282
DOI: 10.1358/dof.2017.042.01.2564104
 
 
Targeting neuroinflammation in the treatment and prevention of Alzheimer's disease
Zenaro, E., Constantin, G.
 
 
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment, language deterioration and visuospatial deficits. The central neuropathological hallmarks of AD are neuronal degeneration, loss of synapses, the formation of neurofibrillary tangles, gliosis and amyloid-beta (Abeta) accumulation. Chronic neuroinflammation is thought to play a role in AD pathology, and numerous studies have indicated that microglia-mediated neuroinflammatory responses promote the neurodegeneration observed in AD. However, vascular inflammation and leukocyte accumulation in the AD brain and in transgenic animals with AD-like pathology suggest a role for new inflammation mechanisms in this disease. Notably, recent animal studies have shown that neutrophils migrate into the AD brain and play an unexpected role in the induction of cognitive deficit and neuropathological changes. Furthermore, blocking LFA-1 integrin, which controls leukocyte-endothelial interactions in AD mice, inhibits both Aß deposition and tau hyperphosphorylation and reduces memory loss. Thus, the emerging role of peripheral leukocytes in the pathogenesis of AD opens new avenues of investigation and may lead to the identification of new therapeutic approaches. This review summarizes our current understanding of the roles of vascular inflammation and circulating leukocytes in AD, focusing on recently discovered neuroinflammation mechanisms. We also discuss a role for adhesion molecules, chemokines and other inflammation mechanisms that may promote brain damage in AD. Given that all current AD therapies are symptomatic, we highlight existing anti-inflammatory treatments as well as novel approaches that may contribute to AD prevention and therapy.


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