Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 326 (5955): 1005-1007

Copyright © 2009 by the American Association for the Advancement of Science

Amyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle

Jae-Eun Kang,1 Miranda M. Lim,1 Randall J. Bateman,1,2,3 James J. Lee,1 Liam P. Smyth,1 John R. Cirrito,1,2 Nobuhiro Fujiki,4 Seiji Nishino,4 David M. Holtzman1,2,3,5,*

Abstract: Amyloid-β (Aβ) accumulation in the brain extracellular space is a hallmark of Alzheimer’s disease. The factors regulating this process are only partly understood. Aβ aggregation is a concentration-dependent process that is likely responsive to changes in brain interstitial fluid (ISF) levels of Aβ. Using in vivo microdialysis in mice, we found that the amount of ISF Aβ correlated with wakefulness. The amount of ISF Aβ also significantly increased during acute sleep deprivation and during orexin infusion, but decreased with infusion of a dual orexin receptor antagonist. Chronic sleep restriction significantly increased, and a dual orexin receptor antagonist decreased, Aβ plaque formation in amyloid precursor protein transgenic mice. Thus, the sleep-wake cycle and orexin may play a role in the pathogenesis of Alzheimer’s disease.

1 Department of Neurology, Washington University, St. Louis, MO 63110, USA.
2 Hope Center for Neurological Disorders, Washington University, St. Louis, MO 63110, USA.
3 Alzheimer’s Disease Research Center, Washington University, St. Louis, MO 63110, USA.
4 Sleep and Circadian Neurobiology Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA 94304, USA.
5 Department of Developmental Biology, Washington University, St. Louis, MO 63110, USA.

* To whom correspondence should be addressed. E-mail: holtzman{at}neuro.wustl.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Shift Work and Cognition in the Nurses' Health Study.
E. E. Devore, F. Grodstein, and E. S. Schernhammer (2013)
Am. J. Epidemiol. 178, 1296-1300
   Abstract »    Full Text »    PDF »
Brain interstitial oligomeric amyloid {beta} increases with age and is resistant to clearance from brain in a mouse model of Alzheimer's disease.
S. Takeda, T. Hashimoto, A. D. Roe, Y. Hori, T. L. Spires-Jones, and B. T. Hyman (2013)
FASEB J 27, 3239-3248
   Abstract »    Full Text »    PDF »
Sex Difference in Daily Rhythms of Clock Gene Expression in the Aged Human Cerebral Cortex.
A. S. P. Lim, A. J. Myers, L. Yu, A. S. Buchman, J. F. Duffy, P. L. De Jager, and D. A. Bennett (2013)
J Biol Rhythms 28, 117-129
   Abstract »    Full Text »    PDF »
Is Verbal Episodic Memory in Elderly with Amyloid Deposits Preserved Through Altered Neuronal Function?.
R. Ossenkoppele, C. Madison, H. Oh, M. Wirth, B. N. M. van Berckel, and W. J. Jagust (2013)
Cereb Cortex
   Abstract »    Full Text »    PDF »
Epigenetic Regulation of Axonal Growth of Drosophila Pacemaker Cells by Histone Acetyltransferase Tip60 Controls Sleep.
S. K. Pirooznia, K. Chiu, M. T. Chan, J. E. Zimmerman, and F. Elefant (2012)
Genetics 192, 1327-1345
   Abstract »    Full Text »    PDF »
Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of {beta}-Amyloid in Mice with Alzheimer's Disease Pathology.
J. H. Roh, Y. Huang, A. W. Bero, T. Kasten, F. R. Stewart, R. J. Bateman, and D. M. Holtzman (2012)
Science Translational Medicine 4, 150ra122
   Abstract »    Full Text »    PDF »
Neurotoxicity of Amyloid {beta}-Protein: Synaptic and Network Dysfunction.
L. Mucke and D. J. Selkoe (2012)
Cold Spring Harb Perspect Med 2, a006338
   Abstract »    Full Text »    PDF »
Synapses and Alzheimer's Disease.
M. Sheng, B. L. Sabatini, and T. C. Sudhof (2012)
Cold Spring Harb Perspect Biol 4, a005777
   Abstract »    Full Text »    PDF »
Tau elevations in the brain extracellular space correlate with reduced amyloid-{beta} levels and predict adverse clinical outcomes after severe traumatic brain injury.
S. Magnoni, T. J. Esparza, V. Conte, M. Carbonara, G. Carrabba, D. M. Holtzman, G. J. Zipfel, N. Stocchetti, and D. L. Brody (2012)
Brain 135, 1268-1280
   Abstract »    Full Text »    PDF »
Dynamic Analysis of Amyloid {beta}-Protein in Behaving Mice Reveals Opposing Changes in ISF versus Parenchymal A{beta} during Age-Related Plaque Formation.
S. Hong, O. Quintero-Monzon, B. L. Ostaszewski, D. R. Podlisny, W. T. Cavanaugh, T. Yang, D. M. Holtzman, J. R. Cirrito, and D. J. Selkoe (2011)
J. Neurosci. 31, 15861-15869
   Abstract »    Full Text »    PDF »
Opposing Synaptic Regulation of Amyloid-{beta} Metabolism by NMDA Receptors In Vivo.
D. K. Verges, J. L. Restivo, W. D. Goebel, D. M. Holtzman, and J. R. Cirrito (2011)
J. Neurosci. 31, 11328-11337
   Abstract »    Full Text »    PDF »
Human apoE Isoforms Differentially Regulate Brain Amyloid-{beta} Peptide Clearance.
J. M. Castellano, J. Kim, F. R. Stewart, H. Jiang, R. B. DeMattos, B. W. Patterson, A. M. Fagan, J. C. Morris, K. G. Mawuenyega, C. Cruchaga, et al. (2011)
Science Translational Medicine 3, 89ra57
   Abstract »    Full Text »    PDF »
Glutaminyl Cyclase Knock-out Mice Exhibit Slight Hypothyroidism but No Hypogonadism: IMPLICATIONS FOR ENZYME FUNCTION AND DRUG DEVELOPMENT.
S. Schilling, S. Kohlmann, C. Bauscher, R. Sedlmeier, B. Koch, R. Eichentopf, A. Becker, H. Cynis, T. Hoffmann, S. Berg, et al. (2011)
J. Biol. Chem. 286, 14199-14208
   Abstract »    Full Text »    PDF »
Alzheimer's Disease: The Challenge of the Second Century.
D. M. Holtzman, J. C. Morris, and A. M. Goate (2011)
Science Translational Medicine 3, 77sr1
   Full Text »    PDF »
GRK5 Deficiency Accelerates {beta}-Amyloid Accumulation in Tg2576 Mice via Impaired Cholinergic Activity.
S. Cheng, L. Li, S. He, J. Liu, Y. Sun, M. He, K. Grasing, R. T. Premont, and W. Z. Suo (2010)
J. Biol. Chem. 285, 41541-41548
   Abstract »    Full Text »    PDF »
Effects of Synaptic Modulation on {beta}-Amyloid, Synaptophysin, and Memory Performance in Alzheimer's Disease Transgenic Mice.
D. Tampellini, E. Capetillo-Zarate, M. Dumont, Z. Huang, F. Yu, M. T. Lin, and G. K. Gouras (2010)
J. Neurosci. 30, 14299-14304
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882