Down syndrome (DS) is a genetic disorder caused by an extra copy of chromosome 21 (trisomy 21 or T21) and is associated with an increased risk of early-onset Alzheimer's disease (AD), also known as DS-associated AD (DSAD). Individuals with DS typically develop amyloid neuropathology in their late-thirties to early-forties and the mean age of onset of clinical dementia is approximately 55 years. Recent advances in AD clinical research have focused on monoclonal antibodies (mAbs) targeting amyloid-β (Aβ) plaques as a potential therapeutic approach. Therefore, there has been guarded enthusiasm about using anti-amyloid mAbs in the prevention/treatment of DSAD. This narrative review and perspective explores the current understanding of amyloid pathology in AD and DSAD, the rationale for using anti-amyloid mAbs in the treatment of DSAD, and the challenges and opportunities for research toward the application of this therapeutic strategy to older adults with DS.
Keywords: Alzheimer’s disease; Down syndrome; amyloid hypothesis; anti-amyloid monoclonal antibodies; bioethics; intellectual disability; trisomy 21.