Stanford ADRC Pilot Research Projects
Year 2, pilot research project 1
Developing the African killifish as a new system to model the age-dependency, genetics, and spread of Alzheimer’s disease
The goal is to develop the African turquoise killifish as a vertebrate system to model the genetics and spread of Alzheimer’s disease. The prime risk factor for Alzheimer’s disease is age itself. The African killifish, with its compressed lifespan, is ideally suited as an in vivo, integrative model to test new concepts of Alzheimer’s disease. Specifically, we will test whether protein aggregates provide a link among genetic risk factors, age, and disease progression. These studies may lead to new models for the study of AD and may help identify ways to prevent protein aggregates in Alzheimer’s disease.
Year 2, pilot research project 2
The impact of Latino values and cultural beliefs on brain donation
The goal is to increase the number of Latinos with dementia who participate in Alzheimer Disease Center brain donation programs. We will use archived data from the National Alzheimer Coordinating Center to develop knowledge of barriers to, and incentives for, brain donation in Latino and non-Latino ethnic groups. We will use these results to develop culturally appropriate outreach materials, which we will then disseminate to Alzheimer’s Disease Centers nationwide.
Year 1, pilot research project 1
Identification of regulators of α-synuclein toxicity using high complexity shRNA and CRISPR/sgRNA screens
Toxic protein species contribute to a range of neurodegenerative diseases. The Gitler and Bassik laboratories have used genome-wide approaches in yeast, mouse and human iPS cells to elucidate new genes, pathways and targets that contribute to RNA-binding protein dysfunction and toxicity. Our goal in this proposal is to apply a powerful, new experimental approach to identify regulators of α-synuclein toxicity are critical for the pathology of synucleinopathies, including Alzheimer’s disease and Parkinson’s disease. The ability to perform genomewide modifier screens (loss- and gain-of-function screens) in mammalian cells (including neurons) has great potential to identify disease-relevant therapeutic targets. Until very recently, performing comprehensive genetic modifier screens in mammalian cells was unfeasible for most laboratories. The Bassik laboratory has helped develop new technologies that allow (1) significant improvements in precision and throughput in genome-wide RNAi screens, and (2) the first systematic pairwise genetic interaction maps in mammalian cells. We will use these tools to integrate broadly with other Stanford ADRC investigators to perform high-throughput genetic screens in mammalian neuronal models.
Year 1, pilot research project 2
Principal investigator: Michael Zeineh, MD, PhD
In Vivo MR microscopic imaging of Alzheimer's disease at 7T
Alzheimer’s disease (AD) is currently not well understood, and studies of amyloid plaques and tau deposition have yet to result in any efficacious treatment. Iron, in concert with amyloid and taum may play a significant role in inflammation, resulting in neurodegeneration. This proposal investigates the inflammatory component of AD in humans. We will use novel ultra-high resolution 7T MRI and push spatial resolution to the level of microns in order to detect iron associated with neurodegeneration. This technique may yield a unique biomarker that assesses the inflammatory component of AD, enabling the screening of pre-clinical patients and clinical trials of novel neurotherapeutics.