Theorizing that the APOE ε4 Variant Increases Alzheimer ' s Risk Through Increased Microglial Inflammation

It is well established that the ε4 variant of APOE increases the risk of Alzheimer's disease, but there is no firm consensus as to why this is the case. Theories abound. Researchers here suggest that the mechanism of interest is increased neuroinflammation, as APOEε4 increases the tendency for the innate immune cells known as microglia to become activated and inflammatory in the aging brain. There has been an increased focus on chronic inflammation in Alzheimer's disease in recent years, particularly given the continued failure to produce meaningful patient benefits via clearance of amyloid-β, with some researchers going so far as to suggest it is the primary driving mechanism in the onset and progression of the condition. Alzheimer's disease (AD) is a multifactorial disorder neuropathologically characterized by amyloid-β (Aβ) plaques and tau neurofibrillary tangles. Among the multiple pathogenic processes involved in AD etiology, neuroinflammation, commonly associated with microglial reactivity, has been increasingly recognized. Microglial activation plays a key role in the accumulation of AD hallmark proteinopathies, rather than being merely an epiphenomenon of their deposition. Specifically, recent observations from animal and human studies suggest that microglial activation precedes and may drive tau spread over the neocortex, from the medial temporal to association and primary sensory structures. Such microglial activation is synaptotoxic, affects brain con...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs