Successes and failures: the latest advances in the clinical development of amyloid–β–targeting monoclonal antibodies for treating Alzheimer's disease

INTRODUCTION: The amyloid cascade hypothesis postulated that the accumulation of amyloid-β (Aβ) was the first step of the Alzheimer's disease (AD) pathological process. Effective reduction of Aβ plaque load by numerous drug candidates, among which anti-Aβ monoclonal antibodies, has produced discussible clinical successes and several failures. It was questioned whether Aβ may be the principal AD pathogenic factor and a valid therapeutic target and if targeting Aβ different species could make the difference. AREAS COVERED: This review article summarized successes and failures of anti-Aβ monoclonal antibody therapy for AD, delineating the latest advances for their clinical development also according to their target engagement and downstream biomarkers. EXPERT OPINION: ) may indicate a potential benefit of anti-Aβ monoclonal antibodies in AD and downstream biomarkers should be considered for providing comprehension in cognitive and clinical efficacy of future AD RCTs.