Idolizing the clearance of Amyloid-β by microglia

With an increasingly aging population, the prevalence of dementia is on the rise. Alzheimer’s disease (AD) is the most common form of dementia, accounting for 60–70% of all cases. AD is characterized by the formation of neurofibrillary tangles of hyper-phosphorylated tau and of beta amyloid (Aβ) aggregates, referred to as plaques. Both are thought to incite neuroinflammation and neurodegeneration, resulting in progressive cognitive decline. The identification of genes involved in Aβ processing, and accumulation of Aβ in familial AD has triggered efforts to develop Aβ-based therapies. However, these have suffered so far from undesired side effects and limited efficacy (1). The lack of a significant decrease in cognitive decline in patients with reduced Aβ plaque-load following immunization against Aβ (2), emphasizes therefore the need to consider other possible pathophysiological mechanisms in AD.