Amyloid β-peptide and Alzheimer's disease

Allsop, David and Mayes, Jennifer (2014) Amyloid β-peptide and Alzheimer's disease. Essays in Biochemistry, 56: 7. pp. 99-110. ISSN 0071-1365

Abstract

One of the hallmarks of Alzheimer’s disease (AD) is the formation of senile plaques in the brain, which contain fibrils composed of the amyloid-β (Aβ) peptide. According to the ‘amyloid cascade’ hypothesis, the aggregation of Aβ 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 Aβ 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 Aβ from the amyloid precursor protein (APP), 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 Aβ, which are still the main hope for providing a more effective treatment for AD in the future.