Dr. Brendan Lucey, MD is a highly-motivated physician-scientist with a strong interest in sleep, aging, and neurodegenerative disorders such as Alzheimer?s disease. He is an Assistant Professor of Neurology (tenure track) at Washington University and is seeking support from this administrative supplement for research costs to explore novel changes in cerebrospinal fluid (CSF) tau, phosphorylated tau (p-tau), and ?-synuclein concentrations with sleep-wake activity and pharmacologic sleep induction via orexin receptor antagonism from suvorexant. Dr. Lucey?s long-term goal is to develop an exciting research program investigating the interrelationships between sleep, aging, and Alzheimer?s disease. Understanding these relationships could drive the development of new treatments to prevent or delay Alzheimer?s disease. This administrative supplement request builds on recently published work and our unpublished preliminary data showing that sleep loss increases concentrations of tau and ?-synuclein in cerebrospinal fluid (CSF) and affects the forms of phosphorylated tau (p-tau). Further, this supplement will leverage novel samples collected as part of the parent grant.
There are no treatments that substantially delay the progression of Alzheimer?s disease. The parent grant of this proposal tests whether poorer sleep efficiency (i.e. sleep quality) increases the production and concentration, while decreasing clearance, of a protein called amyloid-? (A?) in the human central nervous system. A second goal of the study is to test if improving sleep efficiency in individuals with poor sleep quality decreases A? production and concentration in the human central nervous system. In this administrative supplement, we will test other proteins implicated in Alzheimer?s disease pathogenesis to: 1) determine the effect of poor sleep efficiency on CNS tau, p-tau, and ?-synuclein concentrations and tau phosphorylation; and 2) determine the effect of pharmacologic sleep induction on CNS tau, p-tau, and ?-synuclein concentrations and tau phosphorylation.
| Lucey, Brendan P; Hicks, Terry J; McLeland, Jennifer S et al. (2018) Effect of sleep on overnight cerebrospinal fluid amyloid ? kinetics. Ann Neurol 83:197-204 |
| Lucey, Brendan P; Fagan, Anne M; Holtzman, David M et al. (2017) Diurnal oscillation of CSF A? and other AD biomarkers. Mol Neurodegener 12:36 |
