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Principal Investigator  
Principal Investigator's Name: Bernard Fongang
Institution: UT Health San Antonio
Department: Biggs Institute for Alzheimer's and Neurodegenerat
Country:
Proposed Analysis: Gene expression signatures related to vascular cognitive impairment and dementia Genome-Wide Association Studies have identified several genetic risk loci associated with Alzheimer's Disease, but the gene expression changes that contribute to vascular cognitive impairment and all-cause dementia are still not fully understood. The study of gene expression signatures and their regulations provides an unbiased approach for determining the mechanisms by which changes at the DNA level are translated into diseases. We propose to study the gene expression signatures from blood associated with risk of vascular cognitive impairment and all-cause dementia. We will identify changes in gene expression correlated with MRI markers of cerebrovascular disease, cognitive tasks sensitive to vascular impairment, and we will study how these changes are associated with all-cause dementia and Vascular Dementia. To uncover the associated regulatory mechanisms, we will identify the relationship between key transcription factors and target genes and build their regulatory networks. Aim 1: Gene expression changes and MRI markers of cerebral small vessel disease. To correlate gene expression in blood to 1A) periventricular and deep white matter hyperintensities (WMH), 1B) Peak width of skeletonized mean diffusivity, and 1C) Free Water. These MRI markers are novel sensitive measures of brain changes preceding vascular cognitive impairment. Aim 2: Gene expression changes associated with cognition. To study the association between gene expression and makers of cognitive function. We will determine gene expression correlated to 2A) processing speed and executive function (Trails A and B), 2B) visual memory (Visual Reproductions immediate and delayed), 2C) visuospatial orientation (Hooper Visual Organization Test) and general cognitive function. Aim 3: Gene expression and risk of Dementia. To investigate if there is a differential pattern of gene expression in blood associated with all-cause dementia and the subgroup defined with vascular dementia.
Additional Investigators