Abstract Body

The Alzheimer's disease (AD) drug development pipeline has trials of agents with an increasingly diversified repertoire of biological targets and therapeutic mechanisms of action. Growth in understanding of the biology of AD has led to increased activity in drug development for neuroinflammation, synaptic plasticity, bioenergetic and metabolic processes, end neurotransmitter mechanisms. Within each of these categories there is a diversity of targets in mechanisms, submechanisms and networks. Novel therapeutic strategies are evolving in the AD drug development pipeline including vaccines, stem cell therapies, gene therapies, use of antisense oligonucleotides, and epigenetic interventions. Symptomatic therapies are making substantial progress, particularly those targeting neuropsychiatric symptoms. Current clinical trials are assessing treatments for agitation, psychosis, and sleep. The increasing availability of biomarkers to define trial populations, allow risk stratification, facilitate monitoring in the course of trials, demonstrate pharmacodynamic activity of test agents, provide prognostic information at baseline for patients entering try entering trials, provide information for drug responsive subpopulations or individuals at risk for therapeutic for adverse events, and safety have accelerated clinical trials, improved trial methodology, and allowed more confident decisions regarding the biological impact of test agents and their likely therapeutic benefit. Pharmacodynamic biomarkers allow monitoring of target engagement in proof-of-concept trials and provide evidence of disease modification in clinical trials of disease modifying therapies. Anti-amyloid monoclonal antibodies are in late-stage development, and biological and clinical outcome data are becoming available. Drugs and biomarkers currently in clinical trials will transition to a role in clinical care, altering the therapeutic and care landscape.