Abstract
Despite presence of substantial evidence suggesting the pivotal role of amyloid (Aβ) in Alzheimer's disease (AD), very few therapeutic agents have been able to ameliorate the disease. This paved the way for the discovery of antibody-based immunotherapy to ace Aβ clearance and curb neuronal toxicity, resulting in revival of aducanumab, which following its entry into the brain, interacts with the parenchymal amyloid and decreases Aβ concentration, in a dose-dependent manner. However, the surprising approval from the FDA has created a controversy among healthcare professionals, due to Alzheimer's related imaging abnormality (ARIA) and hypersensitivity, serving as backlogs in its acceptance. Therefore, aducanumab is recognised as being “risen from the grave”, accompanied with contrasting statements within the healthcare paradigm. The manuscript provides a collection of data, aiming to elucidate, both the commendable and critical faces, simultaneously intending to gain the attention of the global researchers towards the possibility of disease-modifying therapy in AD. The manuscript discusses the failure of anti-amyloid therapies in AD, that have accelerated the need to find a suitable therapeutic approach, followed by the discussion of timeline and impact of aducanumab in AD models, alongside the controversial judgement raising significant question. Besides, the authors throw some light on the onco-therapeutic implications of the drug approval, which is identified as a significant consequence of the event. The text provides a holistic picture of the drug action, and enlists the considerations for the future, that might be beneficial to both the acceptance of the drug, and the treatment of the disease.
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•The inoperable AD pathology and inability of conventional therapies to provide a complete treatment.•Timeline of aducanumab approval, accompanied with ups and downs from 2007 to 2021.•Action mechanism of this human Ig gamma 1 MAB, in Aβ clearance and curtailing calcium defects in AD.•Optimistic implications for future Onco-therapeutics.•Controversial outcomes in the ENGAGE and EMERGE trials.