Novel therapeutic strategies provide the real test for the amyloid hypothesis of Alzheimer's disease

The amyloid and tangle cascade hypothesis is the dominant explanation for the pathogenesis of Alzheimer's disease (AD). A complete knowledge of the metabolic pathways leading to beta-amyloid (Abeta) production and clearance in vivo and of the pathological events that lead to fibril formation and deposition into plaques is crucial for the development of an 'anti-amyloid' therapeutic strategy. Important advances in this respect have been achieved recently, revealing new candidate drug targets. Among the most promising potential treatments are beta- and gamma-secretase inhibitors, Abeta vaccination, Cu-Zn chelators, cholesterol-lowering drugs and non-steroidal anti-inflammatory drugs. Now, the major question is whether these drugs will work in the clinic.