Nicole Schupf1, Gertrude H Sergievsky. 1. Laboratory of Epidemiology, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA. ns24@columbia.edu
Abstract
BACKGROUND: The high risk for dementia in adults with Down's syndrome has been attributed to triplication and overexpression of the gene for amyloid precursor protein (APP). But the wide variation in age at onset must be due to other risk factors. AIMS: To identify factors which influence age at onset of dementia in Down's syndrome. METHOD: Studies of factors which influence formation of beta-amyloid (Abeta) were reviewed, including atypical karyotypes, susceptibility genotypes, gender and oestrogen deficiency, and individual differences in Abeta peptide levels. RESULTS: The apolipoprotein E epsilon4 allele, oestrogen deficiency and high levels of Abeta1-42 peptide are associated with earlier onset of dementia, while atypical karyotypes and the apolipoprotein E epsilon2 allele are associated with reduced mortality and reduced risk of dementia. CONCLUSIONS: Factors which influence Abeta levels, rather than overexpression of APP, may account for the differences in age at onset of dementia in Down's syndrome.
BACKGROUND: The high risk for dementia in adults with Down's syndrome has been attributed to triplication and overexpression of the gene for amyloid precursor protein (APP). But the wide variation in age at onset must be due to other risk factors. AIMS: To identify factors which influence age at onset of dementia in Down's syndrome. METHOD: Studies of factors which influence formation of beta-amyloid (Abeta) were reviewed, including atypical karyotypes, susceptibility genotypes, gender and oestrogen deficiency, and individual differences in Abeta peptide levels. RESULTS: The apolipoprotein E epsilon4 allele, oestrogen deficiency and high levels of Abeta1-42 peptide are associated with earlier onset of dementia, while atypical karyotypes and the apolipoprotein E epsilon2 allele are associated with reduced mortality and reduced risk of dementia. CONCLUSIONS: Factors which influence Abeta levels, rather than overexpression of APP, may account for the differences in age at onset of dementia in Down's syndrome.
Authors: Giovanna Cenini; Amy L S Dowling; Tina L Beckett; Eugenio Barone; Cesare Mancuso; Michael Paul Murphy; Harry Levine; Ira T Lott; Frederick A Schmitt; D Allan Butterfield; Elizabeth Head Journal: Biochim Biophys Acta Date: 2011-10-08
Authors: Giovanna Cenini; Ada Fiorini; Rukhsana Sultana; Marzia Perluigi; Jian Cai; Jon B Klein; Elizabeth Head; D Allan Butterfield Journal: Free Radic Biol Med Date: 2014-08-20 Impact factor: 7.376
Authors: M A Kingsbury; B Friedman; M J McConnell; S K Rehen; A H Yang; D Kaushal; J Chun Journal: Proc Natl Acad Sci U S A Date: 2005-04-18 Impact factor: 11.205
Authors: Warren B Zigman; Darlynne A Devenny; Sharon J Krinsky-McHale; Edmund C Jenkins; Tiina K Urv; Jerzy Wegiel; Nicole Schupf; Wayne Silverman Journal: Int Rev Res Ment Retard Date: 2008-01-01
Authors: David Powell; Allison Caban-Holt; Gregory Jicha; William Robertson; Roberta Davis; Brian T Gold; Frederick A Schmitt; Elizabeth Head Journal: Neurobiol Aging Date: 2014-02-04 Impact factor: 4.673