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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD035897-25
Application #
8471130
Study Section
Special Emphasis Panel (ZHD1-MRG-C (SW))
Program Officer
Oster-Granite, Mary Lou
Project Start
1998-02-05
Project End
2015-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
25
Fiscal Year
2013
Total Cost
$1,581,747
Indirect Cost
$78,242
Name
Hugo W. Moser Research Institute Kennedy Krieger
Department
Type
DUNS #
155342439
City
Baltimore
State
MD
Country
United States
Zip Code
21205
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
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
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
Janicki, S C; Park, N; Cheng, R et al. (2014) Estrogen receptor α variants affect age at onset of Alzheimer's disease in a multiethnic female cohort. Dement Geriatr Cogn Disord 38:200-13
Zigman, Warren B (2013) Atypical aging in Down syndrome. Dev Disabil Res Rev 18:51-67
Esbensen, Anna J; Mailick, Marsha R; Silverman, Wayne (2013) Long-term impact of parental well-being on adult outcomes and dementia status in individuals with Down syndrome. Am J Intellect Dev Disabil 118:294-309
Janicki, S C; Park, N; Cheng, R et al. (2013) Aromatase variants modify risk for Alzheimer's disease in a multiethnic female cohort. Dement Geriatr Cogn Disord 35:340-6
Xing, Luzhou; Salas, Martha; Zhang, Hong et al. (2013) Creation and characterization of BAC-transgenic mice with physiological overexpression of epitope-tagged RCAN1 (DSCR1). Mamm Genome 24:30-43

Showing the most recent 10 out of 68 publications