A tough trek in the development of an anti-amyloid therapy for Alzheimer's disease: Do we see hope in the distance?

The search for a clinically effective therapy for patients with Alzheimer's disease (AD) has been long and arduous. In some circles the recent US Food and Drug Administration (FDA) approval of the human monoclonal antibody, Aducanumab, was viewed as a welcome advance. However, the administrative decision, in the face of a negative review by the members of the FDA neurology advisory board raised many questions concerning its appropriateness. In response the FDA has modified the conditions under which the drug should be administered. Currently, the etiology of AD remains unknown. Thus, application of therapies based on the still controversial amyloid hypothesis deserves critical scrutiny. While successful animal studies based on the hypothesis have stimulated many clinical trials in humans, none of these have shown statistically clinical benefit, raising ques-tions regarding the intrinsic validity of the hypothesis itself. However, each successive trial has benefited from the experiences of those which preceded it. Given these caveats, the relevance of an apparent beneficial response in a subset of Aducanumab treated study participants must be weighed carefully. There are competing hy-potheses regarding the etiology and pathophysiology responsible for the development of AD, including tau protein aggregation, acetylcholine deficiency, neuroinflammation, among others, all of which remain contro-versial. Nonetheless, the newly approved agent, Aducanumab did show some subtle benefit in some mild AD patients. Understanding the current hypotheses and controversies may help better evaluate the limitations and challenges in anti-amyloid therapy and in exploration of more efficacious therapies in treating patients with AD in the future.

Automated summary

The search for effective therapy for Alzheimer's disease patients has been challenging, with the recent approval of Aducanumab sparking controversy due to questions surrounding its appropriateness. Various hypotheses including amyloid and tau protein aggregation remain controversial, but Aducanumab did show some benefit in mild AD patients. Understanding these hypotheses and controversies is important to evaluate the limitations and challenges in treating AD patients and exploring more efficacious therapies in the future.