Abstract
Alzheimer's disease (AD), the most prevalent neurodegenerative dementia, is caused by the deposition of amyloid beta (Aβ) plaques and neurofibrillary tau tangles in the brain which progressively lead to impaired cognitive function. On July 02, 2024, The Food and Drug Administration (FDA) approved Donanemab, a third Monoclonal antibody (mAbs)—next to aducanumab and lecanemab. Donanemab is a humanized immunoglobulin gamma 1 (IgG1) and targets insoluble Aβ. Donanemab was designed based on the amyloid cascade hypothesis but recent evidence strongly suggest that AD is associated with a multi-factorial pathology (viz., glymphatic clearance, neuroinflammation, mitochondria dysfunction, etc.).This questions the potential of donanemab as a disease modifying agent in the management of AD. This perspective article throws light on Donanemab's recent FDA approval through a translational lens, bridging the gap between Aβ-centric research and real-world clinical outcomes. Deciphering the clinical utility of these therapies directs future bench-to-bedside strategies for personalized Alzheimer's interventions.