Failure, Success, and Future Direction of Alzheimer Drugs Targeting Amyloid-beta Cascade: Pros and Cons of Chemical and Biological Modalities

Alzheimer's disease (AD) is the most prevalent cause of dementia and has become a health concern worldwide urging for an effective therapeutic. The amyloid hypothesis, currently the most pursued basis of AD drug discovery, points the cause of AD to abnormal production and ineffective removal of pathogenic aggregated amyloid-beta (A beta). AD therapeutic research has been focused on targeting different species of A beta in the amyloidogenic process to control A beta content and recover cognitive decline. Among the different processes targeted, the clearance mechanism has been found to be the most effective, supported by the recent clinical approval of an A beta-targeting immunotherapeutic drug which significantly slowed cognitive decline. Although the current AD drug discovery field is extensively researching immunotherapeutic drugs, there are numerous properties of immunotherapy in need of improvements that could be overcome by an equally performing chemical drug. Here, we review chemical and immunotherapy drug candidates, based on their mechanism of modulating the amyloid cascade, selected from the AlzForum database. Through this review, we aim to summarize and evaluate the prospect of A beta-targeting chemical drugs.

Automated summary

Alzheimer's disease is a common cause of dementia, and an effective therapy is urgently needed. The amyloid hypothesis suggests that abnormal production and ineffective removal of amyloid-beta is the cause of AD. While a lot of focus is on immunotherapy, chemical drugs also have potential in clearing pathogenic proteins. This review evaluates and summarizes the prospect of chemical drugs targeting amyloid-beta based on candidates from the AlzForum database.