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Individuals with Down syndrome develop Alzheimer's disease (AD) neuropathology with near conformity in their 4th to 5th decade, and are at a much higher risk of developing AD dementia than are members of the general population. Not all research sites have access to individuals with DS between the ages of 25 and 40; the years when most likely AD neuropathology generally develops. As with other less common genetic abnormalities, DS, with approximately one in every 700 births, can benefit from multi-site collaborative teams in terms of clinical trials and neuropathology repositories, because collaboration is more likely to yield breakthrough results than individual efforts. The intention of the Down Syndrome and Alzheimer's Disease (DS-AD) PIA is to meet two times per year as a group, in order to form a national and hopefully international tissue and clinical repository, to work with the NIH DS connects, to set up a data sharing and clinical trial network, and also to work with industry to identify treatment targets and biomarkers for DS-AD.