Most epidemiologic studies of risk factors for Alzheimer's diseas are limited to clinically diagnosed disease. The proposed study offers the opportunity to integrate pathologic clinical data, and thereby examine the mechanisms through which risk factors for Alzheimer's disease lead to clinical expression of the disease. Preliminary data for two risk factors, the apolipoprotein E Epsilon 4 allele and years of formal education, suggest that they lead to a clinical disease through dissimilar mechanisms. Although both are associated with clinical disease the epsilon 4 allele is related to recognized Alzheimer's disease pathology, but years of formal education is not We will test the hypotheses that the apolipoprotein E epsilon 4 allele alters risk of clinical disease through its association with amyloid deposition and neurofibrillary changes, that years of formal education and female gender alte risk of clinical disease through their association with neuronal counts and synaptic density and that subcortical brain infarctions alter risk of clinical disease by increasing the likelihood that Alzheimer's disease pathology is clinically expressed. The study will also characterize the relation of age to pathologic and clinical expression of disease and describe how age modifies th relation of post-mortem indices to the clinical expression of Alzheimer's disease. The findings from the proposed study may have profound implications for therapeutic intervention and disease prevention. Hypothesis testing requires risk factor information, longitudinal structured quantitative clinica data collected proximate to death and brain tissue. The proposed project will collect new post-mortem data and link it to available risk factor information and clinical data in innovative analyses. The Religious Orders Study (ROS) which performs annual clinical evaluations on more than 650 nuns, priests, and brothers over the age of 65 who have agreed to brain donation after death, provides and ideal source of longitudinal clinical data and of brain tissue fo the proposed project.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Anderson, Dallas
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Rush University Medical Center
United States
Zip Code
Abner, Erin L; Kryscio, Richard J; Schmitt, Frederick A et al. (2017) Outcomes after diagnosis of mild cognitive impairment in a large autopsy series. Ann Neurol 81:549-559
Sohail, Shahmir; Yu, Lei; Schneider, Julie A et al. (2017) Sleep fragmentation and Parkinson's disease pathology in older adults without Parkinson's disease. Mov Disord 32:1729-1737
Dong, Jing; Wyss, Annah; Yang, Jingyun et al. (2017) Genome-Wide Association Analysis of the Sense of Smell in U.S. Older Adults: Identification of Novel Risk Loci in African-Americans and European-Americans. Mol Neurobiol 54:8021-8032
Yu, Lei; Dawe, Robert J; Boyle, Patricia A et al. (2017) Association Between Brain Gene Expression, DNA Methylation, and Alteration of Ex Vivo Magnetic Resonance Imaging Transverse Relaxation in Late-Life Cognitive Decline. JAMA Neurol 74:1473-1480
Mez, Jesse; Chung, Jaeyoon; Jun, Gyungah et al. (2017) Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans. Alzheimers Dement 13:119-129
Boyle, Patricia A; Yu, Lei; Wilson, Robert S et al. (2017) Person-specific contribution of neuropathologies to cognitive loss in old age. Ann Neurol :
Chibnik, L B; White, C C; Mukherjee, S et al. (2017) Susceptibility to neurofibrillary tangles: role of the PTPRD locus and limited pleiotropy with other neuropathologies. Mol Psychiatry :
Yu, Lei; Dawe, Robert J; Buchman, Aron S et al. (2017) Ex vivo MRI transverse relaxation in community based older persons with and without Alzheimer's dementia. Behav Brain Res 322:233-240
Lu, Ake T; Hannon, Eilis; Levine, Morgan E et al. (2017) Genetic architecture of epigenetic and neuronal ageing rates in human brain regions. Nat Commun 8:15353
Jun, Gyungah R; Chung, Jaeyoon; Mez, Jesse et al. (2017) Transethnic genome-wide scan identifies novel Alzheimer's disease loci. Alzheimers Dement 13:727-738

Showing the most recent 10 out of 330 publications