Abstract
Individuals with Down syndrome (DS) are at high risk for developing Alzheimer's disease (AD) pathology and this has provided significant insights into our understanding of the genetic basis of AD. The present review summarizes recent clinical, neuropathologic, imaging, and fluid biomarker studies of AD in DS (DSAD), highlighting the striking similarities, as well as some notable differences, between DSAD and the more common late-onset form of AD (LOAD) in the general population, as well as the much rarer, autosomal-dominant form of AD (ADAD). There has been significant progress in our understanding of the natural history of AD biomarkers in DS and their relationship to clinically meaningful changes. Additional work is needed to clearly define the continuum of AD that has been described in the general population, such as the preclinical, prodromal, and dementia stages of AD. Multiple therapeutic approaches, including those targeting not only β-amyloid but also tau and the amyloid precursor protein itself, require consideration. Recent developments in the field are presented within the context of such efforts to conduct clinical trials to treat and potentially prevent AD in DS.