Figure 1.

Two different conceptualizations of how amyloid-β affects neurological outcomes. A summarizes a preclinical staging scheme for Alzheimer’s disease in which amyloid-β deposition is the initiating event. In this scheme, brain amyloid-β deposition alone constitutes Stage 1 of preclinical Alzheimer’s disease, followed by Stage 2 in which amyloid-β leads to neurodegeneration. In Stage 3, subtle cognitive dysfunction insufficient to establish dementia or mild cognitive impairment, occurs. This scheme posits neurodegeneration as the invariable mediator between amyloid-β and cognition. B suggests an alternative view in which neurodegeneration and amyloid-β are independent processes. Neurodegeneration without amyloid-β has been referred to as suspected non-Alzheimer pathology (SNAP). In this scheme, either neurodegeneration or amyloid-β alone may lead to cognitive dysfunction, although the two together may produce synergistic harmful effects.