Disease-modifying therapies in Alzheimer's disease: anti-amyloid monoclonal antibodies and clinical perspectives

Abstract

Background: Alzheimer's disease is characterized by progressive cognitive decline and the accumulation of beta-amyloid and neurofibrillary tangles in the brain. Traditionally, treatments have only been symptomatic, but anti-amyloid monoclonal antibodies, such as lecanemab and donanemab, are emerging as therapies capable of reducing amyloid plaques and modestly slowing disease progression. Objective: To review and synthesize recent evidence on anti-amyloid monoclonal antibodies in Alzheimer's disease, addressing clinical effects, mechanisms of action, safety, and perspectives for implementation in clinical practice. Methods: This is a systematic review of articles published in the last five years, consulted in the PubMed and VHL (Virtual Health Library) databases, including clinical trials, systematic reviews, and preclinical studies on anti-amyloid monoclonal antibodies in Alzheimer's disease. Cognitive outcomes, beta-amyloid biomarkers, and drug safety were analyzed. The descriptors used included: “Alzheimer’s disease” AND “anti-amyloid monoclonal antibody” AND “lecanemab” AND “donanemab”. Results: Eighteen studies on anti-β-amyloid monoclonal antibodies, primarily lecanemab and donanemab, were selected, encompassing patients with Alzheimer's in the early and moderate stages. Both significantly reduced cerebral β-amyloid deposits, with a modest but consistent deceleration of cognitive and functional decline, as measured by CDR-SB, ADAS-Cog, and ADCOMS. Lecanemab acts on soluble protofibrils and intermediate aggregates, whereas donanemab binds to mature plaques, promoting robust clearance. Safety considerations include ARIA-E and ARIA-H, which are more common in ApoE ε4 carriers but are generally asymptomatic and monitorable. Lecanemab showed a lower incidence of ARIA compared to donanemab. Older agents, such as solanezumab and bapineuzumab, showed limited clinical benefits. The effect is more pronounced when initiated early and in patients with biomolecular confirmation of amyloid. Conclusion: Anti-amyloid monoclonal antibodies represent an advancement in Alzheimer's disease, with evidence of reduced beta-amyloid deposits and the deceleration of cognitive decline. Early use, careful monitoring, and integration with multidimensional strategies can maximize clinical benefits, signaling a new era in the management of the disease.