Amyloid β-peptide and Alzheimer's disease

One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of A beta (amyloid beta-peptide). According to the 'amyloid cascade' hypothesis, the aggregation of A beta initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of A beta and towards smaller and more soluble 'oligomers' as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of A beta from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral A beta, which is still the main hope for providing a more effective treatment for AD in the future.