Amyloid-beta and treatment opportunities for Alzheimer\u27s disease

Proposed treatments of Alzheimer\u27s disease (AD) are most likely to succeed if they are based on an understanding of the complex biology of AD and its effects on cognition. Treatments may target a single or multiple components of the complex pathology of AD with the hope that by affecting an individual component of AD pathology, the disease course can be affected. One such component is amyloid-beta (Abeta), a feature of the senile plaque. Abeta may be critical for inducing the pathology seen in AD. Accumulation of Abeta may result in a cascade of biochemical events leading to neuronal dysfunction, which may present opportunities for intervention at multiple different points to slow disease progression. Treatment may be directed towards decreasing Abeta production, increasing Abeta removal, and decreasing Abeta aggregation. Alternatively, treatment may be directed at more distal pathways by: modulating downstream events possibly due to Abeta such as free radical toxicity, decreasing inflammation, preventing cell membrane damage, restoring calcium homeostasis, preventing excitotoxicity, and blocking the cellular response to injury by inhibiting neuronal apoptosis. This review underscores the complex biology of Abeta specifically looking at the potential targets of therapeutics based on emerging knowledge of this biology