Small “toxic” aggregates of a specific protein can be found in the blood of people who have Alzheimer’s disease as well as people who didn’t have the disease at the time the blood sample was taken but later developed it. [1]
Amyloid beta protein oligomers, or small, misfolded aggregates, are detected by this blood test, which is thought to be what causes Alzheimer’s disease.
Recent cases
In most cases today, patients are only given an Alzheimer’s diagnosis when they show well-known symptoms like memory loss. At that point, the most effective treatments simply halt further symptom progression.
However, research has shown that Alzheimer’s begins years, if not decades, before the cognitive impairments that enable a diagnosis are present.
These seeds are misfolded beta-amyloid proteins that clump together to form oligomers, which are small aggregates.
Those “toxic” oligomers of amyloid beta are thought to progress into Alzheimer’s disease over time through a process that researchers are still attempting to comprehend.
A test that can measure levels of amyloid beta oligomers in blood samples has been developed by a group led by University of Washington researchers.
Their test, which goes by the acronym SOBA, was able to detect oligomers in the blood of Alzheimer’s disease patients, but it was unable to detect them in the majority of people in a control group who did not exhibit any signs of cognitive impairment when blood samples were taken, as reported in a paper that was published the week of December 5 in the Proceedings of the National Academy of Sciences.
However, oligomers were found in the blood of 11 control group members by SOBA.
Ten of these people had records from their follow-up exams, and all of them had been diagnosed years later with mild cognitive impairment or brain pathology that was consistent with Alzheimer’s disease.
In essence, SOBA had identified the toxic oligomers for these ten individuals prior to the onset of symptoms.
Diagnosis
“Clinicians and researchers have been looking for a reliable Alzheimer’s disease diagnostic test that can not only confirm a diagnosis but also detect signs of the disease before cognitive impairment occurs.
According to senior author Valerie Daggett, a UW professor of bioengineering and faculty member in the UW Molecular Engineering & Sciences Institute, “that’s important for individuals’ health and for all the research into how toxic oligomers of amyloid beta go on and cause the damage that they do.”
Here, we demonstrate that SOBA may serve as the foundation for such a test.
The soluble oligomer binding assay, also known as SOBA, makes use of a distinctive feature of the toxic oligomers. An alpha sheet is a structure created when misfolded amyloid beta proteins begin to clump together into oligomers.
Alpha sheets are uncommon in nature, and previous research by Daggett’s group demonstrated that they frequently bind to other alpha sheets. Her team’s synthetic alpha sheet, which can bind to oligomers in blood or cerebrospinal fluid samples, is the core of SOBA.
After that, the test follows standard procedures to ensure that the oligomers that are attached to the test surface are composed of amyloid beta proteins.
The team put SOBA through its paces with blood samples taken from 310 study participants whose medical records and blood samples had previously been made available for Alzheimer’s research.
Subjects were recorded as having no signs of cognitive impairment, mild cognitive impairment, Alzheimer’s disease, or another type of dementia when blood samples were taken.
In the blood of people with mild cognitive impairment and moderate to severe Alzheimer’s disease, SOBA found oligomers. 52 of the study participants’ blood samples, taken years before their deaths, contained toxic oligomers, confirming the autopsy diagnosis of Alzheimer’s disease in 53 of the cases.
SOBA
SOBA additionally identified oligomers in those individuals from the benchmark group who, records show, later created gentle mental weakness.
Toxic oligomers were absent from blood samples taken from other people who remained unaffected in the control group.
SOBA is being developed into a diagnostic test for oligomers by Daggett’s team and scientists at AltPep, a UW spinoff company.
The researchers also demonstrated that toxic oligomers of a different kind of protein linked to Parkinson’s disease and Lewy body dementia could be easily detected using SOBA in the study.
“We are observing that numerous human sicknesses are related with the amassing of harmful oligomers that structure these alpha sheet structures,” said Daggett. ” Parkinson’s disease, type 2 diabetes, and other diseases as well.
Since SOBA recognizes this one-of-a-kind alpha sheet structure. We anticipate that this approach will aid in the research and diagnosis of numerous other “protein misfolding” diseases.
The assay, in Daggett’s opinion, has more potential.
She stated, “We believe that SOBA could aid in the identification of individuals at risk or incubating the disease, as well as serve as a readout of therapeutic efficacy to aid in the development of early Alzheimer’s disease treatments.”
Overview
Dylan Shea, a doctoral candidate in the Molecular Engineering Program of the UW Department of Bioengineering. She is the study’s lead author.
Elizabeth Colasurdo, a VA Puget Sound Health Care System employee, is one of the co-authors. Alec Smith. He is a UW physiology and biophysics research assistant professor; Courtnie Paschall, a UW Medical Scientist Training Program student;
The UW assistant professor of neurology, Dr. Suman Jayadev. Professor of laboratory medicine and pathology at UW, Dr. Dirk Keene; Douglas Galasko, a University of California, San Diego neurosciences professor;
Assistant Professor of Neurological Surgery at the University of Washington, Dr. Andrew Ko; and Ge Li and Dr. Elaine Peskind, both of the VA Puget Sound Health Care System and the UW Department of Psychiatry and Behavioral Sciences.
The Northwest Mental Illness Research, Education, and Clinical Center, the Washington Research Foundation, and the National Institutes of Health provided funding for the study.
