Hypoxia Due to Cardiac Arrest Induces a Time-Dependent Increase in Serum Amyloid β Levels in Humans
2011 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 6, no 12, e28263- p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2011. Vol. 6, no 12, e28263- p.
abdominal aortic aneurysm, risk factors, screening, smoking, ultrasound
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-165063DOI: 10.1371/journal.pone.0028263ISI: 000298369100025PubMedID: 22194817OAI: oai:DiVA.org:uu-165063DiVA: diva2:471594