Role of Peripheral Proteostasis on Brain Aging and Alzheimer's Disease (R01 Clinical Trial Not Allowed)

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The National Institute on Aging (NIA) solicits research projects that would advance our understanding of how protein homeostasis (proteostasis) in peripheral tissues affects brain aging, leading to the development of Alzheimers Disease (AD). Much research on AD has focused on the accumulation of aberrant protein aggregates in the brain, and in particular amyloid and Tau. Formation of aggregates due to mutations encoded in the APP gene or due to hyperphosphorylation, respectively, have been linked to familial AD. The etiology of the more common, sporadic form of AD, is less certain, although aging is considered a major risk for development of the disease. It is known that proteostasis is less efficiently maintained in all tissues with aging, and this may indicate a link between proteostasis in the periphery and the appearance of aging-related diseases and conditions, including the decline in cognitive function, as well as dementia and AD. Therefore, testing for a role of aging-related loss of peripheral proteostasis in the development of AD is the focus of this FOA.

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