There are many active research projects accessing and applying shared ADNI data. Use the search above to find specific research focuses on the active ADNI investigations. This information is requested annually as a requirement for data access.
| Principal Investigator | |
| Principal Investigator's Name: | Matvei Khoroshkin |
| Institution: | UCSF |
| Department: | Biochemistry |
| Country: | |
| Proposed Analysis: | Alzheimer’s disease (AD) is a global public health issue with no effective treatments to prevent the onset and progression of the disease. AD is characterized as a progressive cognitive decline associated with synaptic loss and, eventually, loss of neurons in the brain. However, the mechanisms of disease initiation and progression have remained largely unknown. We have recently discovered that abnormal decay of mRNAs plays a central role in the cellular deficits associated with AD. Specifically, we have found an RNA binding protein as a protective RNA-binding protein that prevents the degradation of mRNAs – a significant number of these RNA binding protein-protected mRNAs encode synaptic transmission proteins. RNA binding protein deficiency in AD is associated with loss of these mRNAs due to accelerated degradation, and RNA binding protein rescue in neuronal cells can partially revert the gene expression changes associated with AD, including the expression of synaptic transmission genes. Together with genetic association of RNA binding protein variants with higher disease risk, these observations strongly suggest that this RNA binding protein is a novel protective factor against AD, and loss of RNA binding protein contributes to synaptic loss. This project seeks to comprehensively characterize the function of RNA binding protein in neurons, the molecular mechanisms that lead to RNA binding protein deficiency in AD, and the molecular mechanisms that mediate the effect of RNA binding protein loss on cellular deficits. By combining novel computational approaches and experimental models, we will map the brain regions and cell types that are affected by dysregulation of RNA binding protein and other gene regulatory factors, identify the genes that are downstream targets of RNA binding protein, characterize the interplay between tau pathology and RNA binding protein loss, and identify small molecules that can counteract the effect of RNA binding protein loss. These studies will provide a comprehensive understanding of the role of RNA binding protein and, more broadly, post-transcriptional programs in AD pathology, and will pave the way for development of new therapeutic strategies. |
| Additional Investigators | |
| Investigator's Name: | Hani Goodarzi |
| Proposed Analysis: | Alzheimer’s disease (AD) is a global public health issue with no effective treatments to prevent the onset and progression of the disease. AD is characterized as a progressive cognitive decline associated with synaptic loss and, eventually, loss of neurons in the brain. However, the mechanisms of disease initiation and progression have remained largely unknown. We have recently discovered that abnormal decay of mRNAs plays a central role in the cellular deficits associated with AD. Specifically, we have found an RNA binding protein as a protective RNA-binding protein that prevents the degradation of mRNAs – a significant number of these RNA binding protein-protected mRNAs encode synaptic transmission proteins. RNA binding protein deficiency in AD is associated with loss of these mRNAs due to accelerated degradation, and RNA binding protein rescue in neuronal cells can partially revert the gene expression changes associated with AD, including the expression of synaptic transmission genes. Together with genetic association of RNA binding protein variants with higher disease risk, these observations strongly suggest that this RNA binding protein is a novel protective factor against AD, and loss of RNA binding protein contributes to synaptic loss. This project seeks to comprehensively characterize the function of RNA binding protein in neurons, the molecular mechanisms that lead to RNA binding protein deficiency in AD, and the molecular mechanisms that mediate the effect of RNA binding protein loss on cellular deficits. By combining novel computational approaches and experimental models, we will map the brain regions and cell types that are affected by dysregulation of RNA binding protein and other gene regulatory factors, identify the genes that are downstream targets of RNA binding protein, characterize the interplay between tau pathology and RNA binding protein loss, and identify small molecules that can counteract the effect of RNA binding protein loss. These studies will provide a comprehensive understanding of the role of RNA binding protein and, more broadly, post-transcriptional programs in AD pathology, and will pave the way for development of new therapeutic strategies. |
