β-amyloid Peptides and Amyloid Plaques in Alzheimer's Disease

Many lines of evidence support that beta-amyloid (A beta) peptides play an important role in Alzheimer's disease (AD), the most common cause of dementia. But despite much effort the molecular mechanisms of how A beta contributes to AD remain unclear. While A beta is generated from its precursor protein throughout life, the peptide is best known as the main component of amyloid plaques, the neuropathological hallmark of AD. Reduction in A beta has been the major target of recent experimental therapies against AD. Unfortunately, human clinical trials targeting A beta have not shown the hoped-for benefits. Thus, doubts have been growing about the role of A beta as a therapeutic target. Here we review evidence supporting the involvement of A beta in AD, highlight the importance of differentiating between various forms of A beta, and suggest that a better understanding of A beta's precise pathophysiological role in the disease is important for correctly targeting it for potential future therapy.