Nicotinamide Adenine Dinucleotide Augmentation to Prevent or Reverse the Progression of Alzheimer’s Disease in People with Down Syndrome

Narrative A tragically large proportion of people with Down syndrome (DS) will exhibit Alzheimer's Disease (AD) neuropathology by the time they are in their mid-thirties, and most will eventually develop clinical signs and symptoms of dementia by age 60. Dementia is one of the most important contributors to mortality and morbidity in adults with DS, and the prevention and treatment of dementia is a high priority for people with DS and their families. Based on the recommendations of the reviewers, we now propose a multiple ascending dose, randomized, placebo-controlled phase 1 trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of nicotinamide mononucleotide  a molecule that has been shown in preclinical models of AD to ameliorate AD neuropathology by targeting multiple mechanisms and an ability to raise NAD+ levels in the brain and engage the target mechanisms.