title: Con: are we ready to translate Alzheimer's disease-modifying therapies to people with down syndrome?
abstract: BACKGROUND
  Adults with Down syndrome develop Alzheimer's disease neuropathology in an age-dependent manner. This unique feature provides an opportunity to test interventions targeted for prevention of Alzheimer's disease neuropathology and dementia in Down syndrome.
  
  
  CONCLUSIONS
  In considering clinical trial designs, however, there are several challenges that we believe will be critical to examine further. These include: accuracy in dementia, mild cognitive impairment and preclinical Alzheimer's disease diagnoses in Down syndrome; clinical trial outcome measures appropriate for individuals with Down syndrome; in vivo imaging outcome measures (and practical considerations); and contributions of medical co-morbidities to disease progression. Also, when studies are designed, the molecular target may appear to be obvious (for example, targeting beta-amyloid pathology), but chromosome 21 has over 200 additional genes that could influence both positive and negative clinical trial outcomes.
  
  
  CONCLUSIONS
  Observational longitudinal studies of aging in Down syndrome will be critically important as there is a need to establish sensitive clinical outcome measures and understand the consequences of gene overexpression in relation to specific interventions.
authors.affiliation: Department of Pharmacology and Nutritional Sciences, Sanders-Brown Center on Aging, University of Kentucky, 203 Sanders-Brown Building, 800 S. Limestone Street, Lexington 40536-0230, KY, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Head
authors.affiliation: Department of Neurology, Sanders-Brown Center on Aging, University of Kentucky, 203 Sanders-Brown Building, 800 S. Limestone Street, Lexington 40536-0230, KY, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt