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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Specialized Center (P50)
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National Institute on Aging Initial Review Group (NIA)
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Phelps, Creighton H
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University of California Irvine
Internal Medicine/Medicine
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United States
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