Speaker
Description
Background: Down syndrome (Trisomy 21) includes triplication of the APP gene, leading to excess amyloid precursor protein and early amyloid plaque formation. Individuals with Down syndrome typically develop plaques in their 40s, and Alzheimer's disease is their leading cause of mortality. APP‑directed interventions may therefore provide substantial clinical benefit in Down syndrome. However, Down Syndrome also involves immunologic and metabolic comorbidities.
Methods: The Alzheimer's Disease Biomarkers-Down Syndrome (ABC-DS) consortium has recruited a population study of over 100 Down Syndrome patients. Participants undergo cognitive testing and multimodal biomarker profiling, including inflammatory, metabolic, and PET‑based amyloid measures.
Results: PET‑derived amyloid measures are the strongest predictors of cognitive decline. Observed accumulation rates indicate that trials with approximately 50 participants per arm should be powered. However, immunologic and metabolic comorbidities may introduce heterogeneity that complicates trials or reveals subgroups requiring additional interventions.
Discussion: Interventions targeting amyloid accumulation in Down Syndrome are urgently needed. In addition to reporting these results, we will also pose forward‑modeling challenges related to immunologic and metabolic dysfunction in Down syndrome.
