Abstract
The most common genetic cause of intellectual and developmental disability is trisomy of human chromosome 21 (trisomy 21) or Down syndrome. Relative to the general population, individuals with Down syndrome heterogeneously experience atypical morphogenesis, a distinct neurocognitive profile, and a unique spectrum of diverse medical conditions that impact every major organ system. How trisomy 21 results in the highly variable manifestations of Down syndrome remains largely unknown and an active area of heavy investigation with therapeutic implications. For example, common inflammatory and metabolic signatures have begun to emerge across various co-occurring conditions in Down syndrome with assorted impacts on diverse yet intertwined organ systems that could directly or indirectly impact brain health. Here, we review current progress, resources, knowledge gaps, and bottlenecks for precision medicine approaches to promote brain health across the lifespan among individuals with Down syndrome within the larger context of research efforts geared towards our other distinct yet intertwined organ systems. Within this framework, we advocate for interdisciplinary pursuit of systems-level biomarkers to facilitate holistic intervention strategies that precisely benefit individuals with trisomy 21 each experiencing Down syndrome in their own unique way. To this end, we quantitatively assess clinical studies that are actively recruiting participants with Down syndrome and provide historical context through summary figures sourced to user-friendly tables that have been curated from federal websites to empower efficient exploration of research opportunities for interdisciplinary collaborations.