Aducanumab for Alzheimer disease: the amyloid hypothesis moves from bench to bedside

For decades, a battle has raged in the Alzheimer disease (AD) research community. On one side, adherents to the amyloid hypothesis, an evolving body of evidence that abnormal accumulation and aggregation of beta-amyloid (A beta) peptides (the main component of amyloid plaques) plays a key role in triggering a cascade of pathological events that leads to the clinical syndrome of AD dementia (1). On the other side, opponents contend that amyloid deposition is an epiphenomenon that has distracted the field from the true causes of AD, which remain generally obscure. Nearly indisputable human genetics data, as well as considerable biochemical, histological, and animal model evidence, point to A beta as a critical player in AD. Furthermore, brain amyloid can be detected at least 15 years prior to the onset of cognitive symptoms in AD and is associated with substantially increased risk of developing AD dementia in the ensuing decade (2), shaping the concept of a long preclinical or asymptomatic stage of AD (3). Removing amyloid is generally considered a highly promising target for primary and secondary prevention of clinical disease, and the first presymptomatic trials are now ongoing. However, the relationship between amyloid pathology, neurodegeneration, and dementia in AD is complex, as clinico-pathological correlation studies have demonstrated that neither the regional distribution nor the burden of amyloid plaques correlate well with the [...]