Innate immune activation in Alzheimer’s disease

Alzheimer's disease (AD) is known as the most predominant cause of dementia among the aged people. Previously, two hallmarks of AD pathology including extracellular amyloid-beta (A beta) deposition and neurofibrillary tangles (NFTs) inside neurons have been identified. With a better understanding of this disease, neuroinflammation has been a focus, and as its initial event, innate immune activation plays an indispensable role. In brain, as an endogenous stimulator, extracellular A beta deposition activates innate immunity through binding to the pattern recognition receptors (PRR), thus leading to the production and release of substantial inflammatory mediators (NO and ROS) and cytokines (IL-1 beta, IL-10, IL-33 and TNF-alpha) contributing to the development of AD. Epidemiologic evidence has suggested an affirmative influence of non-steroidal anti-inflammatory drugs (NSAIDs) on delaying the progression of AD. Therefore, blocking the inflammatory process may be an effective way to delay or even cure AD. In this review, we mainly elucidate the mechanism underlying these immune responses in AD pathogenesis and attempt to seek the therapeutic methods targeting neuroinflammation.