Hypoxia Due to Cardiac Arrest Induces a Time-Dependent Increase in Serum Amyloid β Levels in Humans

Autor: Kaj Blennow, Brian A. Pink, Erik Mörtberg, David Fournier, Sten Rubertsson, Gail K. Provuncher, Lei Chang, Ray E. Meyer, Andrew J. Rivnak, David H. Wilson, Purvish P. Patel, Evan P. Ferrell, David M. Rissin, Henrik Zetterberg, Linan Song, Todd G. Campbell, Kaitlin A. Minnehan, Cheuk W. Kan, David C. Duffy, Tomasz Piech
Rok vydání: 2011
Předmět:
Proteomics
Male
Postmortem studies
Critical Care and Emergency Medicine
Time Factors
Myocardial Infarction
lcsh:Medicine
Cardiovascular
Biochemistry
Pathogenesis
Patient Admission
Blood plasma
Pathology
Amyloid precursor protein
Medicine
Hypoxia
lcsh:Science
Aged
80 and over
Multidisciplinary
biology
Physics
Amyloidosis
Brain
Middle Aged
Intensive Care Units
Neurology
Biological Assay
Female
medicine.symptom
Alzheimer's disease
Research Article
Adult
medicine.medical_specialty
Cerebrovascular Diseases
Resuscitation
Biophysics
Ischemia
Vascular Dementia
Protein Chemistry
Diagnostic Medicine
Alzheimer Disease
Internal medicine
Humans
Biology
Aged
Amyloid beta-Peptides
business.industry
lcsh:R
Proteins
Hypoxia (medical)
medicine.disease
Peptide Fragments
Heart Arrest
Endocrinology
biology.protein
Dementia
lcsh:Q
business
Protein Abundance
Biomarkers
General Pathology
Zdroj: PLoS ONE, Vol 6, Iss 12, p e28263 (2011)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: