Analytical Methods for Donanemab: A Therapeutic Antibody for Alzheimer's Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia, marked by memory loss, cognitive decline, and functional impairment. Its pathology is characterized by extracellular amyloid- β (Aβ) plaques, intracellular neurofibrillary tangles formed by hyperphosphorylated tau, synaptic loss, and chronic neuroinflammation. Genetic factors, including mutations in APP, PSEN1, and PSEN2 and the presence of the APOE ε4 allele, increase disease risk, particularly in early-onset AD. Despite extensive research, current therapies mainly offer symptomatic relief. Donanemab, a monoclonal antibody targeting pyroglutamate-modified Aβ, represents a disease-modifying approach by promoting amyloid plaque clearance in early Alzheimer’s disease. Clinical trials demonstrate significant amyloid reduction and modest slowing of cognitive decline, with amyloid-related imaging abnormalities as key safety concerns. Biomarker-driven analytical methods, including edema and microhemorrhages, requiring careful monitoring. Combining amyloid-targeted therapy with interventions addressing tau pathology, neuroinflammation, and vascular dysfunction represents a promising multi-modal approach to more effectively modify disease progression.