Current advances and unmet needs in Alzheimer's disease trials for individuals with Down syndrome: Navigating new therapeutic frontiers
Por:
Barroeta, I, Videla, L, Carmona-Iragui, M, Fortea, J, Rafii, MS
Publicada:
1 jun 2025
Resumen:
Individuals with Down syndrome (DS) have a genetically determined form of Alzheimer's disease (AD) due to the amyloid precursor protein (APP) gene dose effect. Nearly all individuals with DS develop AD pathology by age 40. Although dementia is rare before this age, its incidence rises sharply thereafter. Longitudinal studies estimate a lifetime dementia risk exceeding 90%, with prevalence reaching 88%-100% after age 65-a marked contrast to 10%-15% in the general population. Recent breakthroughs in sporadic AD, including anti-amyloid therapies such as lecanemab and donanemab, have shown efficacy in slowing progression. However, individuals with DS were excluded from these trials, leaving critical gaps in safety and efficacy data. This perspective highlights the current state of AD clinical trials in DS, key challenges-(including ethical considerations, recruitment barriers, and cognitive assessment adaptations), and emerging research efforts. Addressing these gaps is essential to ensure equitable access to disease-modifying therapies for individuals with DS.
Filiaciones:
Barroeta, I:
Univ Autonoma Barcelona, Inst Invest Biomed St Pau Hosp St Pau, St Pau Memory Unit, Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Videla, L:
Univ Autonoma Barcelona, Inst Invest Biomed St Pau Hosp St Pau, St Pau Memory Unit, Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Fundacio Catalana Sindrome, Barcelona Med Ctr, Barcelona, Spain
Carmona-Iragui, M:
Univ Autonoma Barcelona, Inst Invest Biomed St Pau Hosp St Pau, St Pau Memory Unit, Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Fundacio Catalana Sindrome, Barcelona Med Ctr, Barcelona, Spain
Fortea, J:
Univ Autonoma Barcelona, Inst Invest Biomed St Pau Hosp St Pau, St Pau Memory Unit, Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Fundacio Catalana Sindrome, Barcelona Med Ctr, Barcelona, Spain
Rafii, MS:
Univ Southern Calif, Keck Sch Med, Alzheimers Therapeut Res Inst, San Diego, CA USA
Green Submitted, hybrid
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