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Science 29 August 2008:
Vol. 321. no. 5893, pp. 1221 - 1224
DOI: 10.1126/science.1161591
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Reports

Amyloid-β Dynamics Correlate with Neurological Status in the Injured Human Brain

David L. Brody,1,2*{dagger} Sandra Magnoni,3* Kate E. Schwetye,1,2 Michael L. Spinner,1,2 Thomas J. Esparza,1,2 Nino Stocchetti,3,4 Gregory J. Zipfel,5 David M. Holtzman1,2

The amyloid-β peptide (Aβ) plays a central pathophysiological role in Alzheimer's disease, but little is known about the concentration and dynamics of this secreted peptide in the extracellular space of the human brain. We used intracerebral microdialysis to obtain serial brain interstitial fluid (ISF) samples in 18 patients who were undergoing invasive intracranial monitoring after acute brain injury. We found a strong positive correlation between changes in brain ISF Aβ concentrations and neurological status, with Aβ concentrations increasing as neurological status improved and falling when neurological status declined. Brain ISF Aβ concentrations were also lower when other cerebral physiological and metabolic abnormalities reflected depressed neuronal function. Such dynamics fit well with the hypothesis that neuronal activity regulates extracellular Aβ concentration.

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 Department of Anesthesia and Intensive Care, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via Sforza n 35, 20100 Milan, Italy.
4 Milan University, Milan, Italy.
5 Department of Neurological Surgery, Washington University, St. Louis, MO 63110, USA.

* These authors contributed equally to this work.

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

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease.
R. L. Buckner, J. Sepulcre, T. Talukdar, F. M. Krienen, H. Liu, T. Hedden, J. R. Andrews-Hanna, R. A. Sperling, and K. A. Johnson (2009)
J. Neurosci. 29, 1860-1873
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Science. ISSN 0036-8075 (print), 1095-9203 (online)