Plos One | December 14, 2011

Henrik Zetterberg, Erik Mortberg, Linan Song, Lei Chang, Gail K. Provuncher, Purvish P. Patel, Evan Ferrell, David R. Fournier, Cheuk W. Kan, Todd G. Campbell, Ray Meyer, Andrew J. Rivnak, Brian A. Pink, Kaitlin A. Minnehan, Tomasz Piech, David M. Rissin, David C. Duffy, Sten Rubertsson, David H. Wilson, Kaj Blennow
PlosOne
DOI:10.1371/journal.pone.0028263

Abstract: Amyloid b (Ab) 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 Ab accumulation in familial AD, less is known about the cause(s) of brain amyloidosis in sporadic disease. Animal and postmortem studies suggest that Ab 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 Ab42 concentration in 25 resuscitated patients with severe hypoxia due to cardiac arrest. After a lag period of 10 or more hours, very clear serum Ab42 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 Ab levels in blood. The results point to the possibility that hypoxia may play a role in the amyloidogenic process of AD.