Title | Orexin-A is Associated with Increases in Cerebrospinal Fluid Phosphorylated-Tau in Cognitively Normal Elderly Subjects. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Osorio RS, Ducca EL, Wohlleber ME, Tanzi EB, Gumb T, Twumasi A, Tweardy S, Lewis C, Fischer E, Koushyk V, Cuartero-Toledo M, Sheikh MO, Pirraglia E, Zetterberg H, Blennow K, Lu S-E, Mosconi L, Glodzik L, Schuetz S, Varga AW, Ayappa I, Rapoport DM, de Leon MJ |
Journal | Sleep |
Volume | 39 |
Issue | 6 |
Pagination | 1253-60 |
Date Published | 2016 06 01 |
ISSN | 1550-9109 |
Keywords | Aged, Aging, Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Biomarkers, Cognition, Educational Status, Female, Humans, Magnetic Resonance Imaging, Male, Orexins, Peptide Fragments, Phosphorylation, Regression Analysis, Sleep, Sleep Apnea Syndromes, tau Proteins, Time Factors |
Abstract | STUDY OBJECTIVES: To evaluate the role of orexin-A with respect to cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers, and explore its relationship to cognition and sleep characteristics in a group of cognitively normal elderly individuals. METHODS: Subjects were recruited from multiple community sources for National Institutes of Health supported studies on normal aging, sleep and CSF biomarkers. Sixty-three participants underwent home monitoring for sleep-disordered breathing, clinical, sleep and cognitive evaluations, as well as a lumbar puncture to obtain CSF. Individuals with medical history or with magnetic resonance imaging evidence of disorders that may affect brain structure or function were excluded. Correlation and linear regression analyses were used to assess the relationship between orexin-A and CSF AD-biomarkers controlling for potential sociodemographic and sleep confounders. RESULTS: Levels of orexin-A, amyloid beta 42 (Aβ42), phosphorylated-tau (P-Tau), total-tau (T-Tau), Apolipoprotein E4 status, age, years of education, reported total sleep time, number of awakenings, apnea-hypopnea indices (AHI), excessive daytime sleepiness, and a cognitive battery were analyzed. Subjects were 69.59 ± 8.55 years of age, 57.1% were female, and 30.2% were apolipoprotein E4+. Orexin-A was positively correlated with Aβ42, P-Tau, and T-Tau. The associations between orexin-A and the AD-biomarkers were driven mainly by the relationship between orexin-A and P-Tau and were not influenced by other clinical or sleep characteristics that were available. CONCLUSIONS: Orexin-A is associated with increased P-Tau in normal elderly individuals. Increases in orexin-A and P-Tau might be a consequence of the reduction in the proportion of the deeper, more restorative slow wave sleep and rapid eye movement sleep reported with aging. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT01962779. |
DOI | 10.5665/sleep.5846 |
Alternate Journal | Sleep |
PubMed ID | 26951396 |
PubMed Central ID | PMC4863214 |
Grant List | R01 AG022374 / AG / NIA NIH HHS / United States R01 HL111724 / HL / NHLBI NIH HHS / United States R01 AG013616 / AG / NIA NIH HHS / United States R01 HL118624 / HL / NHLBI NIH HHS / United States P30 AG008051 / AG / NIA NIH HHS / United States K24 HL109156 / HL / NHLBI NIH HHS / United States R21 AG049348 / AG / NIA NIH HHS / United States |
Related Institute:
Brain Health Imaging Institute (BHII)