Alzheimer disease (AD) is the leading cause of age-related dementia, affecting over 5 million people in the United States alone. Unfortunately, current therapies are largely palliative and several promising drug candidates have failed in late-stage clinical trials. Hence, there is an urgent need to improve our understanding of the basic mechanisms that drive the development of AD and to develop new and effective therapies. Preclinical AD research has thus far relied heavily on transgenic mouse models but recent advances in stem cell biology have opened up an exciting new opportunity to model AD and test therapeutics with patient-derived human cells. Stem cell research is a major strength of the UCI ADRC as we were the first to show improved cognition in transgenic models of AD with neural stem cell transplantation and to use human embryonic stem cells to examine AD-associated mutations. The UCI ADRC therefore proposes the establishment of the first AD induced pluripotent stem (IPS) cell core. The goals of this core will be to generate, validate, and distribute a well-powered collection of AD, MCI, and control IPS cell lines to researchers within the UCI ADRC, within the whole ADC program, and worldwide. The significant advantage of having this core be part of the ADRC is that each cell line is linked to corresponding multi-dimensional clinical, biomarker, and pathological datasets. Hence, the IPS cell will provide scientists with a powerful, novel and innovative approach to understand the genetic and phenotypic basis of sporadic AD and identify and evaluate novel disease-modifying therapeutic interventions. To achieve these goals, the IPS cell core proposes the following 4 specific aims:
AIM 1 : Isolate, expand, and bank primary skin fibroblasts and peripheral blood mononuclear source cells from ADRC clinical cohort subjects.
AIM 2 : Generate integration-free IPS lines from fibroblasts of ADRC subjects.
AIM 3 : Validate, characterize, and expand ADRC iPS cell clones.
AIM 4 : Distribute ADRC iPS cell lines to investigators and facilitate access to corresponding clinical, biomarker, and pathological datasets.

Public Health Relevance

Stem cell research is changing the way we study human disease. The ability to examine disease mechanisms and therapies in primary human cells represents a paradigm shift in preclinical research. Huge strides are indeed being made in the study of human disorders through the use of patient-derived IPS cells. It seems only appropriate that this powerful approach be adopted and incorporated into the ADC Program to study a disease that afflicts so many and for which traditional research avenues have thus far failed.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
3P50AG016573-14S1
Application #
8551184
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Phelps, Creighton H
Project Start
2000-04-15
Project End
2015-03-31
Budget Start
2013-09-30
Budget End
2014-03-31
Support Year
14
Fiscal Year
2013
Total Cost
$447,598
Indirect Cost
$149,098
Name
University of California Irvine
Department
Internal Medicine/Medicine
Type
Organized Research Units
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Wang, Tingyan; Qiu, Robin G; Yu, Ming (2018) Predictive Modeling of the Progression of Alzheimer's Disease with Recurrent Neural Networks. Sci Rep 8:9161
Agogo, George O; Ramsey, Christine M; Gnjidic, Danijela et al. (2018) Longitudinal associations between different dementia diagnoses and medication use jointly accounting for dropout. Int Psychogeriatr 30:1477-1487
Hainsworth, A H; Lee, S; Foot, P et al. (2018) Super-resolution imaging of subcortical white matter using stochastic optical reconstruction microscopy (STORM) and super-resolution optical fluctuation imaging (SOFI). Neuropathol Appl Neurobiol 44:417-426
Alosco, Michael L; Sugarman, Michael A; Besser, Lilah M et al. (2018) A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer's Disease Neuropathology. J Alzheimers Dis 63:1347-1360
Brent, Robert J (2018) Estimating the monetary benefits of medicare eligibility for reducing the symptoms of dementia. Appl Econ 50:6327-6340
Deming, Yuetiva; Dumitrescu, Logan; Barnes, Lisa L et al. (2018) Sex-specific genetic predictors of Alzheimer's disease biomarkers. Acta Neuropathol 136:857-872
Cox, Chelsea G; Ryan B A, Mary M; Gillen, Daniel L et al. (2018) A Preliminary Study of Clinical Trial Enrollment Decisions Among People With Mild Cognitive Impairment and Their Study Partners. Am J Geriatr Psychiatry :
Tse, Kai-Hei; Cheng, Aifang; Ma, Fulin et al. (2018) DNA damage-associated oligodendrocyte degeneration precedes amyloid pathology and contributes to Alzheimer's disease and dementia. Alzheimers Dement 14:664-679
Crum, Jana; Wilson, Jeffrey; Sabbagh, Marwan (2018) Does taking statins affect the pathological burden in autopsy-confirmed Alzheimer's dementia? Alzheimers Res Ther 10:104
Schaffert, Jeff; LoBue, Christian; White, Charles L et al. (2018) Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer's disease. Neuropsychology 32:410-416

Showing the most recent 10 out of 518 publications