The Early Events That Initiate β-Amyloid Aggregation in Alzheimer's Disease

Alzheimer's disease (AD) is characterized by the development of amyloid plaques and neurofibrillary tangles (NFTs) consisting of aggregated beta-amyloid (A beta) and tau, respectively. The amyloid hypothesis has been the predominant framework for research in AD for over two decades. According to this hypothesis, the accumulation of A beta in the brain is the primary factor initiating the pathogenesis of AD. However, it remains elusive what factors initiate A beta aggregation. Studies demonstrate that AD has multiple causes, including genetic and environmental factors. Furthermore, genetic factors, many age-related events and pathological conditions such as diabetes, traumatic brain injury (TBI) and aberrant microbiota also affect the aggregation of A beta. Here we provide an overview of the age-related early events and other pathological processes that precede A beta aggregation.