Researchers Review the Amyloid Hypothesis Potential to Yield a Therapy for Alzheimer’s Disease

Patrícia Silva, PhD avatar

by Patrícia Silva, PhD |

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Researchers at the University of Glasgow recently published in the journal Future Science OA a comprehensive review regarding the inhibition of beta-amyloid production as a therapeutic strategy for patients with Alzheimer’s disease. The study is entitled “The role and therapeutic targeting of α-, β— and γ-secretase in Alzheimer’s disease.

Alzheimer’s disease is a neurodegenerative disorder where individuals initially experience memory loss and confusion that gradually leads to behavior and personality changes, a decline in cognitive abilities, and ultimately the severe loss of mental function. The disease is characterized by the loss of neurons responsible for memory and learning, and brain formation of amyloid plaques [aggregates of beta-amyloid proteins derived from the amyloid precursor protein (APP)]. Alzheimer’s disease is estimated to affect more than 36 million individuals worldwide, being the most common form of dementia in the elderly population. Currently there are no drugs available to either stop or stabilize disease progression.

The so-called “amyloid hypothesis” suggests that the accumulation of beta-amyloid proteins within brain tissues is the trigger event for Alzheimer’s disease development, and therefore it should be inhibited. In this review, the research team analyzed studies where the formation of beta-amyloid proteins was inhibited by interfering with the activity of specific proteolytic secretases that transform APP into beta-amyloid, and assess whether this approach is a viable strategy for Alzheimer’s treatment.

“This review outlines the role of the proteolytic secretases to produce beta amyloid peptide as part of the “Amyloid Hypothesis” of Alzheimer’s disease,” said the authors in a news release. “We examine the current status of the secretases as therapeutic targets in Alzheimer’s disease and speculate as to the viability of the Alzheimer’s disease hypothesis as a whole in light of recent findings.”

The research team suggests that one cannot be certain that targeting secretases linked to APP processing will provide the groundbreaking therapy urgently needed to treat Alzheimer’s disease. In fact, due to several set-backs and clinical trial failures with drugs targeting the secretases, large pharmaceutical companies have withdrawn part of their investment in this area.

According to the team, the amyloid hypothesis has been the main therapeutic approach in the last two decades, and advocates of the theory argue that studies so far have not properly tested the hypothesis and that the negative results obtained in clinical trials might be explained by other factors, such as drug side effects or ineffective drug targeting of the secretases. The team believes that despite the recent failures in clinical trials, the secretase targeting approach might still be a viable therapeutic option that needs to be further explored.

“With the many failures we have seen in drugs targeting APP processing and the continued socioeconomic burden of Alzheimer’s Disease, it is excellent to see such a comprehensive review covering research in the area and discussing potential ways forward,” concluded the Managing Editor of Future Science OA, Francesca Lake.