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Hypoxia due to cardiac arrest induces a time-dependent increase in serum amyloid β levels in humans

Zetterberg, H; Mörtberg, E; Song, L; Chang, L; Provuncher, GK; Patel, PP; Ferrell, E; ... Blennow, K; + view all (2011) Hypoxia due to cardiac arrest induces a time-dependent increase in serum amyloid β levels in humans. PLoS One , 6 (12) , Article e28263. 10.1371/journal.pone.0028263. Green open access

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Abstract

Amyloid β (Aβ) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aβ accumulation in familial AD, less is known about the cause(s) of brain amyloidosis in sporadic disease. Animal and postmortem studies suggest that Aβ secretion can be up-regulated in response to hypoxia. We employed a new technology (Single Molecule Arrays, SiMoA) capable of ultrasensitive protein measurements and developed a novel assay to look for changes in serum Aβ42 concentration in 25 resuscitated patients with severe hypoxia due to cardiac arrest. After a lag period of 10 or more hours, very clear serum Aβ42 elevations were observed in all patients. Elevations ranged from approximately 80% to over 70-fold, with most elevations in the range of 3-10-fold (average approximately 7-fold). The magnitude of the increase correlated with clinical outcome. These data provide the first direct evidence in living humans that ischemia acutely increases Aβ levels in blood. The results point to the possibility that hypoxia may play a role in the amyloidogenic process of AD.

Type: Article
Title: Hypoxia due to cardiac arrest induces a time-dependent increase in serum amyloid β levels in humans
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0028263
Publisher version: http://dx.doi.org/10.1371/journal.pone.0028263
Language: English
Additional information: © 2011 Zetterberg et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3237426
Keywords: Adult, Aged, Aged, 80 and over, Amyloid beta-Peptides, Anoxia, Biological Assay, Brain, Female, Heart Arrest, Humans, Intensive Care Units, Male, Middle Aged, Patient Admission, Peptide Fragments, Resuscitation, Time Factors
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1411914
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