Alzheimer dementia (AD) is an increasingly prevalent cognitive disorder affecting older adults. It is associated with significantly degraded quality of life for AD patients and caregivers alike, increasing expenses, morbidity, and mortality. It has been demonstrated that urinary incontinence is present in at least 1/3 of AD patients, and is a direct contributor to institutionalization of the AD patient. Since AD is the most common neurodegenerative disease and incontinence has been regarded as a result of poor brain control over urinary function, it is important to understand the neuronal linkages between these two diseases. This proposal aims to understand how neuronal dysfunction arising from abnormal generation or accumulation of β-amyloid peptide (Aβ) impacts bladder functions in the AD patient. More relevantly, structural changes such as amyloid deposition, formation of neuritic plaque and neurofibrillary/tau occur in the brain preceding cognitive decline by typically two decades, a similar structural “lead-time” may exist in the bladder as well. These changes, if present, might offer a pathway to a feasible biomarker of early AD pathology in asymptomatic persons. In this exploratory project, we will use multiple lines of established mouse AD models to test the hypothesis that a specific AD structural and functional bladder phenotype exists. Secondarily, we will begin to test the temporal relationship of bladder structure and function in the AD mouse vs. wild type mouse, and whether modulating structural changes will affect function. The results of this project will therefore either confirm the existing brain-centric model of AD pathophysiology, or expand the pathophysiologic model to include peripheral pathology important to disease expression.