PIs:
Adam Fleisher, M.D., M.A.S.
Richard Caselli, M.D.
Eric Reiman, M.D.
Contact persons:
Kathryn Demarco: [email protected]
Candy Monarrez: [email protected]
Contact method: please contact site directly
VRADB Application required for sample access? No
Study Description:
This ongoing longitudinal research program uses FDG PET, PiB and florbetapir PET, structural, resting state functional connectivity MRI, CSF and plasma samples, genome-wide association (GWA) data, and a battery of clinical ratings and neuropsychological tests to detect and track the brain and cognitive changes associated with three levels of genetic risk for Alzheimer’s disease (AD) in cognitively normal, initially late-middle-aged persons with two, one or no copies of the the apolipoprotein E (APOE) ε4 allele, the major AD susceptibility gene. It aims to help characterize the changes associated with the preclinical stages of AD, to contribute to the evaluation of genetic and non-genetic risk factors using preclinical imaging endophenotypes, and to lay a foundation for the accelerated evaluation of treatments to prevent AD using biomarker and sensitive cognitive endpoints. Participants have detailed cognitive, imaging and fluid biomarker analyses every two years (amyloid and FDG PET, MRI and lumbar puncture).
Subjects:
Participants provide their informed consent, provide blood samples for APOE genotypes, and understand they will not receive information about their genetic test results. Individuals with 2, 1 and no copies of the APOE4 allele are initially matched for their age, gender and educational level and followed with our battery of tests every two years using our imaging and cognitive assessments. Many of the individuals have had GWA data and plasma and serum samples. A small but growing number have begun to have CSF samples (12ml per collection).
Collection Method: Blood and CSF collected as per site procedures.
Storage: Plasma, Serum, and CSF samples are all stored in a -80°C freezer.
Other measurements available for this cohort:
We encourage researchers to reach out to us, explore collaborative opportunities and use our resource of data and samples in support of our shared scientific goals.
Related Publications:
Caselli, R. J., Dueck, A. C., Osborne, D., Sabbagh, M. N., Connor, D. J., Ahern, G. L. et al. (2009). Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect.N.Engl.J.Med., 361,255-263.
Caselli, R. J., Graff-Radford, N. R., Reiman, E. M., Weaver, A., Osborne, D., Lucas, J. et al. (1999). Preclinical memory decline in cognitively normal apolipoprotein E-epsilon4 homozygotes.Neurology., 53,201-207.
Reiman, E. M., Caselli, R. J., Chen, K., Alexander, G. E., Bandy, D., & Frost, J. (2001). Declining brain activity in cognitively normal apolipoprotein E varepsilon 4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease.Proc Natl Acad Sci U S A, 98,3334-3339.
Reiman, E. M., Caselli, R. J., Yun, L. S., Chen, K., Bandy, D., Minoshima, S. et al. (1996). Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E.N Engl J Med, 334,752-758.
Reiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D. et al. (2004). Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia.Proc Natl Acad Sci U S A, 101,284-289.
Reiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D. et al. (2005). Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism.Proc.Natl.Acad.Sci.U.S.A, 102,8299-8302.
Reiman, E. M., Chen, K., Liu, X., Bandy, D., Yu, M., Lee, W. et al. (2009). Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease.Proc.Natl.Acad.Sci.U.S.A, 106,6820-6825.