Affiliations: [a] Department of Neurosciences, University of California-San Diego, San Diego, CA, USA | [b] Sun Health Research Institute, Sun City, AZ, USA | [c] San Diego VAMC, San Diego, CA, USA
Correspondence:
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Corresponding author: Marwan Sabbagh, M.D., Center for Clinical Research, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351, USA, Tel.: +1 623 875 6500, Fax: +1 632 875 6504
Abstract: Proposed treatments of Alzheimer's 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-ß (Aß), a feature of the senile plaque. Aß may be critical for inducing the pathology seen in AD. Accumulation of Aß 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 Aß production, increasing Aß removal, and decreasing Aß aggregation. Alternatively, treatment may be directed at more distal pathways by: modulating downstream events possibly due to Aß 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 Aß specifically looking at the potential targets of therapeutics based on emerging knowledge of this biology.
