Neuroimaging and Neuropathology of Alzheimer’s Disease in Down Syndrome

Evaluating cerebrovascular pathologies in people with Down syndrome using high-resolution, high-contrast postmortem neuroimaging

Why do individuals with Down syndrome develop Alzheimer’s disease decades earlier than the general population? This proposal will use high-resolution imaging and postmortem brain samples from well-characterized cohorts of adults with Down syndrome and late-onset Alzheimer’s disease. By identifying imaging biomarkers and clarifying early disease mechanisms, we aim to advance understanding of Alzheimer’s in Down syndrome, promote inclusive research, and guide effective interventions to improve diagnostics and treatment strategies.

Our team in Pittsburgh serves as the central site for postmortem imaging of Down syndrome autopsy cases nationwide through the Alzheimer’s Biomarker Consortium – Down Syndrome. We will leverage high-resolution MRI with advanced segmentation and registration methods to co-register with antemortem neuroimages and postmortem histology in the same subjects. Quantitative assessments of postmortem white matter abnormalities near amyloid-positive regions will highlight cerebrovascular pathologies in Down syndrome compared to a late-onset Alzheimer’s disease cohort from our Research Center.

We aim to identify several neuroimaging features—both spatial patterns and protein biomarkers—to inform future research involving larger cohorts and investigate the utility of these biomarkers in the short term. Ultimately, this work may shed light on early events in Alzheimer’s disease progression and enable more effective interventions tailored to the needs of people with Down syndrome.