Summary: A new blood test can detect the toxic beta-amyloid oligomers associated with Alzheimer’s disease years before symptoms appear.
Source: University of Washington
Today, by and large, patients are only diagnosed with Alzheimer’s after showing well-known signs of the disease, such as memory loss. At this point, the best treatment options simply slow the progression of symptoms.
But research has shown that the seeds of Alzheimer’s disease are planted years, if not decades, earlier, long before cognitive impairment emerges and makes a diagnosis possible. These seeds are beta-amyloid proteins that fold up and stick together, forming small aggregates called oligomers. Over time, through a process scientists are still trying to understand, these “toxic” beta-amyloid oligomers are thought to develop into Alzheimer’s.
A team led by researchers from the University of Washington has developed a laboratory test capable of measuring levels of beta-amyloid oligomers in blood samples.
As they report in an article published the week of December 5 in the Proceedings of the National Academy of Sciencestheir test – known by the acronym SOBA – could detect oligomers in the blood of patients with Alzheimer’s disease, but not in most members of a control group who showed no signs of cognitive impairment at the time of blood samples were taken.
However, SOBA detected oligomers in the blood of 11 individuals in the control group. Follow-up examination records were available for 10 of those people, and all were diagnosed years later with mild cognitive impairment or brain pathology compatible with Alzheimer’s disease. Essentially, for these 10 people, SOBA had detected the toxic oligomers before the onset of symptoms.
“What clinicians and researchers have wanted is a reliable diagnostic test for Alzheimer’s disease – and not just a test that confirms a diagnosis of Alzheimer’s, but one that can also detect signs of the disease before that cognitive impairment does not occur. This is important for the health of individuals and for all research into how toxic amyloid-beta oligomers continue and cause the damage they do,” said lead author Valerie Daggett, professor of bio- engineering at UW and a faculty member at UW Molecular Engineering & Sciences. Institute.
“What we show here is that SOBA can be the basis for such a test.”
SOBA, which stands for soluble oligomer binding assay, exploits a unique property of toxic oligomers. When misfolded beta-amyloid proteins begin to clump together into oligomers, they form a structure known as an alpha sheet.
Alpha sheets are not commonly found in nature, and previous research by Daggett’s team has shown that alpha sheets tend to bind to other alpha sheets. At the heart of SOBA is a synthetic alpha sheet designed by his team that can bind to oligomers in cerebrospinal fluid or blood samples. The test then uses standard methods to confirm that the oligomers attached to the test surface are made of beta-amyloid proteins.
The team tested SOBA on blood samples from 310 research subjects who had previously made their blood samples and some of their medical records available for Alzheimer’s disease research. At the time the blood samples were taken, the subjects were recorded as showing no signs of cognitive impairment, mild cognitive impairment, Alzheimer’s disease or any other form of dementia.
SOBA has detected oligomers in the blood of people with mild cognitive impairment and moderate to severe Alzheimer’s disease. In 53 cases, the research subject’s Alzheimer’s diagnosis was verified after death by autopsy – and the blood samples of 52 of them, which had been taken years before their death, contained toxic oligomers.
SOBA also detected oligomers in members of the control group who, according to the records, later developed mild cognitive impairment. Blood samples from other individuals in the control group that remained intact lacked toxic oligomers.
Daggett’s team is working with scientists from AltPep, a UW spin-off company, to develop SOBA into a diagnostic test for oligomers. In the study, the team also showed that SOBA could easily be modified to detect toxic oligomers of another type of protein associated with Parkinson’s disease and dementia with Lewy bodies.
“We find that many human diseases are associated with the accumulation of toxic oligomers that form these alpha-sheet structures,” Daggett said. “Not only Alzheimer’s disease, but also Parkinson’s disease, type 2 diabetes and more. SOBA picks up on this unique alpha sheet structure, so we hope this method can help diagnose and study many other “protein misfolding” diseases.
Daggett thinks the test has additional potential.
“We believe SOBA could help identify those at risk of or incubating the disease, as well as serve as a readout of therapeutic efficacy to aid in the development of early treatments for Alzheimer’s disease,” he said. she declared.
The study’s lead author is Dylan Shea, a doctoral student in the Molecular Engineering Program in the UW Department of Bioengineering. Co-authors are Elizabeth Colasurdo of VA Puget Sound Health Care System; Alec Smith, assistant research professor at UW in physiology and biophysics; Courtnie Paschall, a student in the UW Medical Scientist Training Program; Dr. Suman Jayadev, assistant professor of neurology at UW; Dr. Dirk Keene, UW professor of laboratory medicine and pathology; Douglas Galasko, professor of neuroscience at the University of California, San Diego; Dr. Andrew Ko, assistant professor of neurological surgery at UW; and Ge Li and Dr. Elaine Peskind, both of the UW Department of Psychiatry and Behavioral Sciences and the VA Puget Sound Health Care System. The research was funded by the National Institutes of Health, the Washington Research Foundation and the Northwest Mental Illness Research, Education and Clinical Center.
About this Alzheimer’s disease research news
Author: James Urton
Source: University of Washington
Contact: James Urton – University of Washington
Image: Image is in public domain
Original research: The findings will appear in PNAS
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