Diseases that mimic Alzheimer's disease (AD) are understudied causes of cognitive impairment in the elderly. Perhaps the most common and high-morbidity "AD mimic" is HS-Aging. HS-Aging pathology afflicts a rapidly expanding demographic group: persons of advanced old age. HS-Aging pathology is observed in 10-25% of individuals over age 85 in multiple large autopsy series. The novelty of this work is in providing a new mechanism for an intervention to target a common human brain disease. Our work is based on the first genomewide scan to determine the gene(s) that confer risk for HS-Aging; this scan indicated that a "druggable target" (ABCC9) is the key risk gene. At the end of this research program we hope to have produced the first animal model of HS-Aging pathology, good data about whether sulfonylureas exacerbate HS-Aging pathology, and publishable preclinical data about the first possible therapeutic strategy for HS-Aging. We have every intention to move this potential therapeutic into full preclinical development and eventual clinical studies for HS-Aging if our project is successful.