Monoclonal antibody therapy in Alzheimer’s disease: an overview and vision

Prior attempts to treat Alzheimer’s disease have been limited to improving the function of cholinergic or glutamatergic synapses and have been largely palliative. The advent of monoclonal antibody (MAb) therapies has allowed researchers to directly test the amyloid hypothesis, that targeting the extracellular aggregation of amyloid-β (Aβ) plaques will arrest the progression of neurodegeneration. MAb therapy stimulates a patient’s immune system to eliminate Aβ plaques and thus slows the neurodegenerative progression of the disease. In this review the authors will discuss the successes and limitations of MAb therapy and the efficacy and mechanism of different treatments. The key risk associated with Mab therapy is amyloid-related imaging abnormalities that can coincide with cerebral effusion or siderosis. Deposits of Aβ oligomers can adhere to capillaries, and it is thought that immune activation targeting these oligomers can result in adverse events. With proper screening of high-risk patients (determined by either genetic testing for Aβ42/40 or cardiovascular profile), severe side effects can potentially be mitigated. This assessment of current MAb approaches concludes that progress in the neurodegeneration field will be contingent upon shifting the diagnostic framework to focus on early detection and prevention of the neurodegenerative cascade initiated by Aβ plaque formation.