The program of research focusing on adults with Down syndrome (DS), ongoing since 1987, will be continued, now consisting of four projects supported by three cores. While all of the projects have clear origins in the program's current activities, several new initiatives are included. The investigators will: (a) determine if individual differences in risk for Alzheimer's disease (AD) within the elderly population with DS is associated with insulin resistance and other features of metabolic syndrome;(b) develop empirically validated methods for identifying the presence of mild cognitive impairment (MCI) in adults with DS, differentiating this condition from cognitive changes associated with developmentally appropriate aging, per se;(c) determine the role of altered patterns of DNA methylation in DS pathogenesis and variation in phenotypic expression within this population, including selected aging-related processes;and (d) use independent datasets to evaluate the relations between age at onset of AD (as well as related phenotypic characteristics) and single nucleotide polymorphisms (SNPs) of approximately 60 candidate genes located on chromosome 21 as well as other chromosomes. As in the past, goals will be achieved through extensive collaborations among investigators representing multiple disciplines. Common assessment procedures, repeated at intervals of approximately 18 months, will be employed to characterize in detail the health, cognitive, and functional status of each of the 300 adults with DS actively participating in the program. Findings and biological samples from previous studies will also be available for the genetic and epigenetic studies now being proposed, bringing the total projected sample size to 788 adults with DS. Cognitive and functional changes will be related to selected biomarkers as well as genetic and epigenetic findings, providing a far richer description of this population than could occur in the context of any single research project. Findings should provide clear insights into: (a) mechanisms underlying important features of the DS phenotype, (b) individual differences in those features, (c) factors modifying risk for dementia, and (d) assessment methods that can inform diagnostic decisions relatively early in disease progression. Further, some findings may have direct implications for promoting more successful aging for adults with DS.
Down syndrome is the most prevalent cause of intellectual disability, affecting one in 733 babies born in the U.S. It causes a characteristic phenotype that includes atypical aging and increased risk for Alzheimer's disease (AD). Life expectancy has increased dramatically for this population in recent years, and there is need to develop more effective strategies for addressing age-associated health concerns, especially AD.
| Schupf, Nicole; Lee, Joseph H; Pang, Deborah et al. (2018) Epidemiology of estrogen and dementia in women with Down syndrome. Free Radic Biol Med 114:62-68 |
| Babulal, Ganesh M; Quiroz, Yakeel T; Albensi, Benedict C et al. (2018) Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need. Alzheimers Dement : |
| Esbensen, Anna J; Hooper, Stephen R; Fidler, Deborah et al. (2017) Outcome Measures for Clinical Trials in Down Syndrome. Am J Intellect Dev Disabil 122:247-281 |
| Do, Catherine; Xing, Zhuo; Yu, Y Eugene et al. (2017) Trans-acting epigenetic effects of chromosomal aneuploidies: lessons from Down syndrome and mouse models. Epigenomics 9:189-207 |
| Lee, Joseph H; Lee, Annie J; Dang, Lam-Ha et al. (2017) Candidate gene analysis for Alzheimer's disease in adults with Down syndrome. Neurobiol Aging 56:150-158 |
| Jenkins, Edmund C; Ye, Lingling; Krinsky-McHale, Sharon J et al. (2016) Telomere longitudinal shortening as a biomarker for dementia status of adults with Down syndrome. Am J Med Genet B Neuropsychiatr Genet 171B:169-74 |
| Mendioroz, Maite; Do, Catherine; Jiang, Xiaoling et al. (2015) Trans effects of chromosome aneuploidies on DNA methylation patterns in human Down syndrome and mouse models. Genome Biol 16:263 |
| Schupf, Nicole; Lee, Annie; Park, Naeun et al. (2015) Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome. Neurobiol Aging 36:2907.e1-10 |
| Krinsky-McHale, Sharon J; Silverman, Wayne; Gordon, James et al. (2014) Vision deficits in adults with Down syndrome. J Appl Res Intellect Disabil 27:247-63 |
| Hobbs, Charlotte A; Chowdhury, Shimul; Cleves, Mario A et al. (2014) Genetic epidemiology and nonsyndromic structural birth defects: from candidate genes to epigenetics. JAMA Pediatr 168:371-7 |
Showing the most recent 10 out of 73 publications
