title: Down syndrome and beta-amyloid deposition.
abstract: OBJECTIVE
  Exciting new therapeutic approaches to the treatment or prevention of Alzheimer's disease involve preventing, slowing or reversing beta-amyloid accumulation. These interventions may also apply to the treatment of Alzheimer's disease in Down syndrome. The purpose of the current review is therefore to summarize developments and advances in our understanding of beta-amyloid pathogenesis in Down syndrome over the past year.
  
  
  RESULTS
  A shift in research to a focus on early events in beta-amyloid pathogenesis in Down syndrome has led to several novel observations. Several authors have reported the accumulation of both soluble and intracellular beta-amyloid before extracellular beta-amyloid (senile plaques) in Down syndrome. Increases in beta-amyloid levels in Down syndrome may reflect the increased expression and protein levels of beta-site amyloid precursor protein cleavage enzyme 2 on chromosome 21. The impact of the accumulation of beta-amyloid may have differential effects on development and aging in Down syndrome.
  
  
  CONCLUSIONS
  The past year has seen significant advances in our understanding of beta-amyloid pathogenesis and the functional consequences of beta-amyloid accumulation in Down syndrome. However, there are still large gaps in our knowledge of the pathways involved in beta-amyloid degradation and clearance. It will be critical to conduct clinical trials to test therapeutic strategies that may reduce beta-amyloid in Down syndrome directly to determine the optimal age and dose for specific interventions. Given the differences in the mechanism of beta-amyloid accumulation in Down syndrome, careful consideration needs to be given to potential clinical trials to treat this disorder.
authors.affiliation: Institute for Brain Aging and Dementia, Department of Neurology, University of California, Irvine, California, USA. ehead@uci.edu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Head
authors.forename: Ira T
authors.initials: IT
authors.lastname: Lott
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D028226:Amyloidosis, Familial / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D001921:Brain / Q000473:pathology; D002648:Child; D002891:Chromosomes, Human, Pair 21; D004314:Down Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D015227:Lipid Peroxidation / Q000235:genetics / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases