title: Hypoxia due to cardiac arrest induces a time-dependent increase in serum amyloid β levels in humans.
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.
authors.affiliation: Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. henrik.zetterberg@clinchem.gu.se
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Erik
authors.initials: E
authors.lastname: Mörtberg
authors.forename: Linan
authors.initials: L
authors.lastname: Song
authors.forename: Lei
authors.initials: L
authors.lastname: Chang
authors.forename: Gail K
authors.initials: GK
authors.lastname: Provuncher
authors.forename: Purvish P
authors.initials: PP
authors.lastname: Patel
authors.forename: Evan
authors.initials: E
authors.lastname: Ferrell
authors.forename: David R
authors.initials: DR
authors.lastname: Fournier
authors.forename: Cheuk W
authors.initials: CW
authors.lastname: Kan
authors.forename: Todd G
authors.initials: TG
authors.lastname: Campbell
authors.forename: Ray
authors.initials: R
authors.lastname: Meyer
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Rivnak
authors.forename: Brian A
authors.initials: BA
authors.lastname: Pink
authors.forename: Kaitlin A
authors.initials: KA
authors.lastname: Minnehan
authors.forename: Tomasz
authors.initials: T
authors.lastname: Piech
authors.forename: David M
authors.initials: DM
authors.lastname: Rissin
authors.forename: David C
authors.initials: DC
authors.lastname: Duffy
authors.forename: Sten
authors.initials: S
authors.lastname: Rubertsson
authors.forename: David H
authors.initials: DH
authors.lastname: Wilson
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000097:blood*; D001681:Biological Assay; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D006323:Heart Arrest / Q000097:blood* / Q000150:complications*; D006801:Humans; D000860:Hypoxia / Q000097:blood* / Q000209:etiology*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D010343:Patient Admission; D010446:Peptide Fragments / Q000097:blood*; D012151:Resuscitation; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)