Significant elevations in blood levels of amyloid beta 42 peptide were detected by Single Molecule Array (SiMoA) technology in patients who experienced hypoxia following cardiac arrest, according to results presented this week at the American Academy of Neurology annual meeting held in Honolulu.
SiMoA technology is based upon the isolation of individual immunocomplexes on beads using standard enzyme-linked immunosorbent assay (ELISA) reagents. Beads with or without labeled immunocomplexes are loaded into arrays containing femtoliter-sized wells and the arrays are sealed in the presence of the enzyme substrate and fluorescently imaged.
The ability of SiMoA to measure extremely low abundance proteins has enabled discovery of a direct link between brain injury caused by hypoxia and increased amyloid beta 42 levels in blood, according to David Wilson, PhD, senior director, product development at Quanterix (Cambridge, Mass.), and colleagues.
The amyloid beta 42 testing was conducted at Quanterix on serum samples obtained from 26 resuscitated patients who were admitted to the department of surgical sciences, anesthesia and intensive care at Uppsala University in Uppsala, Sweden.
In the study, all 26 patients exhibited a significant elevation of amyloid beta 42, ranging from approximately 50 percent to over 30-fold, according to Wilson and colleagues.
"These data are the first to show a correlation between hypoxic stress and the upregulation of amyloid beta 42 in humans. The findings also indicate that amyloid beta 42 levels after cardiac arrest correlate with long-term cognitive outcome. The study highlights the potential of SiMoA to illuminate disease pathways involving proteins present at previously undetectable levels," said Wilson.
"From an Alzheimer's perspective, these findings are very exciting," stated Kaj Blennow, MD, PhD, study co-author and professor in clinical neurochemistry at the University of Gothenburg in Molndal, Sweden. "Mild ischemia due to arteriolosclerosis is common in the elderly, and more common in Alzheimer's patients, and one possibility is that this will result in chronic upregulation of amyloid beta 42, leading to plaque deposits in the brain. These findings should stimulate further study into the relevance of mild, chronic ischemia as a trigger for the amyloid cascade in Alzheimer's disease pathogenesis," added Blennow.