In the 2015-2020 funding cycle, the UCI ADRC is supporting the following three major projects.
High-Resolution Neuroimaging Biomarkers for Preclinical Alzheimer’s Disease
Project Leader: Michael A. Yassa, Ph.D.
A critical goal of biomedical research is establishing indicators of preclinical AD (i.e. biomarkers) allowing for early diagnosis and intervention. Our project combines: 1) novel high-resolution magnetic resonance imaging (MRI) tools, 2) novel cognitive tests particularly sensitive to memory processes in the hippocampus and 3) assessments of beta-amyloid (Aβ) pathology, in order to better understand preclinical AD and identify mechanistic biomarkers. We will test the validity of biomarker candidates in two special cohorts as models of early susceptibility to AD (Down syndrome – DS) and late resistance (nondemented 90+).
Microglia as Mediators of Dendritic Spine Loss and Plaque Formation in the AD Brain
Project Leader: Kim Green, Ph.D.
Dendritic spine loss is closely associated with cognitive decline in Alzheimer’s disease (AD) and other disorders. Identifying the mechanisms and stimuli that lead to spine loss in disease is crucial to developing strategies to reverse or prevent these losses, hopefully leading to improvements in cognition. Concurrent with spine loss, chronic microglial-activation is found in the AD brain and in other disorders. Our project will utilize human tissue to explore the relationship between microglia and dendritic spine loss, as well as plaque formation, in AD. Utilizing novel technology, we will be able to fully study the relationship between human microglia and AD pathology/spine loss in a fashion that has not been previously possible. These results will potentially lead to the development of inhibitors that can eliminate microglia in the AD brain and hence prevent spine loss.
The Role of ApoE in Neuroplasticity and Ab Clearance using iPS Cell-Derived Astrocytes
Project Leader: Wayne Poon, Ph.D.
The goal of this project is to understand the molecular mechanisms associated with the apoe4 genetic risk factor that is associated with late-onset Alzheimer’s disease, the most common form of this type of dementia. This project will use novel techniques to reprogram or convert patient skin cells to astrocytes, a type of cell present in the brain with many supportive functions including the regulation of brain cell-to-cell communication, also known as synaptic plasticity. The objectives are to determine why individuals who carry this genetic risk are susceptible to cognitive decline with age and to identify novel therapeutic targets that can eventually lead to viable AD treatments in the near future.