Evolution and the scientific method

Alzheimer’s disease (AD) is a devastating age related disease that currently effects as many as 4 million Americans. It has, and as the “graying” of America proceeds, will continue to have a dramatic impact on our social, health and economic capabilities. Although we have made immense progress in the understanding of the disease, its cure has yet to be realized. In 1906 Alois Alzheimer described unusual clumps and tangled fibers in the brain of a deceased woman. These clumps and tangles are now known to be deposits of amyloid(A ) and neurofibrillary tangles (NFT) of hyperphosphorylated tau respectively. These features remain the defining characteristics of the AD brain and understanding their relationship to the progression of the disease will almost certainly be key to finding a cure for AD. Deposits of A , or plaques, in addition to being a key morphologic feature of the AD brain, have been a driving force guiding much of the AD research of the past several decades. This body of work has led to what is now known as the “amyloid hypothesis.” This hypothesis states that progressive accumulation of A within the brain initiates a complicated cascade of events that ultimately results in neuronal dysfunction and loss [14]. This cascade involves multiple cell types and signal transduction pathways that result in a wide variety of functional and structural changes in the brain. In this review, Robinson and Bishop take an alternative look at the existing data and propose a “bioflocculant hypothesis” for the function of A in normal aging as well as in the AD brain. This hypothesis proposes that A functions as a neuroprotectant by binding to extracellular neurotoxic solutes. A then precipitates into plaques thereby capturing these toxic agents and presenting them for efficient phagocytic removal. Much of the review and criticism of the data supporting the amyloid hypothesis presented by Robinson and Bishop focuses on the role of mature A plaques in the pathogenesis of AD. However, as the amyloid hypothesis has evolved, focus into the toxic role of A has turned from these mature