The National Academy of Sciences/National Research Council Twin Registry (""""""""the Registry"""""""") contains approximately 4,300 living pairs of white male twins who will be aged 72-83 in 2000. This competing renewal application proposes studies in the Registry that, combined with work to date, will yield 240 twin pairs in which one or both members have Alzheimer's disease (AD). This population-based panel will enable the continued investigation of four broad aims: 1) Estimate the magnitude of genetic influences on the development and age of onset of AD by contrasting concordance rates and the similarity of onsets within monozygotic (MZ) and dizygotic (DZ) pairs; 2) Characterize the environmental contribution of variability of onset of AD. For example, variability of onset within MZ pairs defines the maximum degree to which the environmental influences can modify the onset of AD; 3) Evaluate the role of specific genes on the development and age of onset of AD using the Sibling Transmission/Disequilibrium Test approach to investigate the association between candidate genes such as alpha-2 macroglobulin (A2M) and AD; and 4) Identify environmental factors that are associated with the risk of developing AD, using the co-twin control method. The research will capitalize upon recent developments in the genetics of AD, specifically the influence of apolipoprotein E (APOE) genotype and candidate gene A2M on both liability to AD and its timing of onset. Such findings can be used to refine the classical twin paradigm of investigating broad (but heterogeneous) genetic and environmental influences. Thus, one can not only estimate the heritability of AD in general, but also undertake partitioned analyses to estimate the phenotypic variance attributable to genotypes at APOE or other marker systems, as these are identified. However, until all of the genes that predispose to AD are identified, the twin method has several advantages over other approaches in identifying the extent of the genetic and environmental contribution to AD. Several MZ twin pairs have been described with widely divergent onsets of AD. Environmental factors may therefore alter the onset, and hence the populations risk, of some genetically defined forms of AD. This study will analyze the environmental contribution to variability of onset, and will characterize the divergence in onset within sets of genetically matched individuals. Since comprehensive information on environmental factors has been collected on all participating members of the twin registry, this study will also employ the co-twin control method to seek the specific environmental factors that may be responsible for this variation. A population-based twin design remains the ideal approach to these sorts of investigations.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Epidemiology and Disease Control Subcommittee 2 (EDC)
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Anderson, Dallas
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Duke University
Schools of Medicine
United States
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Oh, Gabriel; Ebrahimi, Sasha; Wang, Sun-Chong et al. (2016) Epigenetic assimilation in the aging human brain. Genome Biol 17:76
Arden, Rosalind; Luciano, Michelle; Deary, Ian J et al. (2016) The association between intelligence and lifespan is mostly genetic. Int J Epidemiol 45:178-85
Gurland, Barry J; Page, William; Small, Brent et al. (2015) Heritability of Health and Aging Limitations on Personally Desired Activities. Health Psychol Res 3:1981
McArdle, John J; Plassman, Brenda L (2009) A biometric latent curve analysis of memory decline in older men of the NAS-NRC twin registry. Behav Genet 39:472-95
Wang, C Sheei-Meei; Burke, J R; Steffens, D C et al. (2009) Twin pairs discordant for neuropathologically confirmed Lewy body dementia. J Neurol Neurosurg Psychiatry 80:562-5
Jarvik, Lissy; LaRue, Asenath; Blacker, Deborah et al. (2008) Children of persons with Alzheimer disease: what does the future hold? Alzheimer Dis Assoc Disord 22:6-20
Carlson, Michelle C; Helms, Michael J; Steffens, David C et al. (2008) Midlife activity predicts risk of dementia in older male twin pairs. Alzheimers Dement 4:324-31
Potter, Guy G; Helms, Michael J; Plassman, Brenda L (2008) Associations of job demands and intelligence with cognitive performance among men in late life. Neurology 70:1803-8
Potter, Guy G; Helms, Michael J; Burke, James R et al. (2007) Job demands and dementia risk among male twin pairs. Alzheimers Dement 3:192-199
Holsinger, Tracey; Helms, Michael; Plassman, Brenda (2007) Intelligence in early adulthood and life span up to 65 years later in male elderly twins. Age Ageing 36:286-91

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