4.8 Article

Amyloid-β dynamics correlate with neurological status in the injured human brain

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SCIENCE
卷 321, 期 5893, 页码 1221-1224

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1161591

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  1. NIH [NS049237, AG13956]
  2. Burroughs Wellcome Career Award in the Biomedical Sciences
  3. Cure Alzheimer's Fund

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The amyloid-beta peptide (A beta) 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 A beta concentrations and neurological status, with A beta concentrations increasing as neurological status improved and falling when neurological status declined. Brain ISF A beta 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 A beta concentration.

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