Researchers from the University of Washington developed a laboratory test that can measure toxic amyloid proteins – known as amyloid beta oligomers – in blood samples and potentially detect Alzheimer’s disease years before symptoms develop.
According to a report published in the Proceedings of the National Academy of Sciences, the test is called “soluble oligomer binding assay” – or SOBA – and it can detect toxic oligomers in the blood of patients with Alzheimer’s disease.
Oligomers are a soluble protein species; however, they’re deformed and toxic to cells, Karen Sullivan, PhD, ABPP, a board-certified neuropsychologist and expert in Alzheimer’s, dementia and brain health, told Seasons.
Toxic oligomers also lead to a variety of “downstream effects,” including impaired neuronal signaling, neurodegeneration and neuroinflammation that can begin 10 to 20 years before the start of symptoms, the authors wrote.
“Over the last 10 to 15 years, evidence has accumulated that amyloid oligomers play a key role in the earliest stages of how Alzheimer’s disease develops,” she said. “That is, these oligomers set up in the brain and damage neurons before the amyloid plaques.”
The SOBA test works by specifically targeting a unique property of the toxic oligomers. When misfolded amyloid beta proteins begin to clump together into oligomers, they form a structure known as an “alpha sheet” (α-sheet).
Past research showed that alpha sheets tend to stick to other alpha sheets, so the team designed the SOBA test to use a makeshift or synthetic alpha sheet that can bind to alpha sheet oligomers in samples of either cerebrospinal fluid or blood. The SOBA test then uses standard methods to confirm that the toxic oligomers attached to the test surface are made up of amyloid beta proteins.
“α-sheet is a nonstandard protein structure discovered in molecular dynamics (MD) simulations of a variety of amyloid-disease associated proteins,” the authors wrote. “We reasoned that this structure may represent a unique target for early detection, and we designed stable, soluble, nontoxic α-sheet peptides to complement the α-sheet structure in toxic species.”
What did the researchers find?
The research team used the SOBA test on blood samples from 310 participants who had previously made some of their medical records and blood samples available for Alzheimer’s research. When blood samples were taken from the participants, they were also identified as having either no signs of cognitive impairment, mild cognitive impairment, Alzheimer’s disease (AD) or another form of dementia.
The test was able to detect oligomers in the blood of participants with mild cognitive impairment and moderate to severe Alzheimer’s. The authors stated that for about 53 cases, the participants’ diagnosis of Alzheimer’s was confirmed after death by an autopsy. In addition, they found that blood samples for 52 of them, taken as a sample years before their deaths, contained toxic oligomers.
The test was also able to detect oligomers in some participants who were in the control group, who had later developed mild cognitive impairment. Furthermore, they found blood samples that were taken from other individuals in the control group who did not have any cognitive impairment lacked the toxic oligomers.
“These results suggest that SOBA can detect early Alzheimer’s disease pathology,” the authors said. “Early detection and disease-modifying treatments are necessary to combat Alzheimer’s disease … A first step in that process is early diagnosis to intervene before irreparable damage occurs, which is estimated to begin 10 to 20 years before the presentation of symptoms.”
Early detection and disease-modifying treatments are necessary to combat Alzheimer’s disease…
Valerie Daggett, PhD, senior author of the study, said in a statement the SOBA test can also be used to differentiate between other amyloid diseases, such as Parkinson’s.
“We are finding that many human diseases are associated with the accumulation of toxic oligomers that form these alpha sheet structures. Not just Alzheimer’s, but also Parkinson’s, type 2 diabetes and more,” she said. “SOBA is picking up that unique alpha sheet structure, so we hope that this method can help in diagnosing and studying many other ‘protein misfolding’ diseases.”
What comes next?
Researchers are currently working with scientists to develop SOBA into a diagnostic test for oligomers. Future studies, however, are needed to replicate, validate and extend the findings from their study.
“We believe that SOBA could aid in identifying individuals at risk or incubating the disease, as well as serve as a readout of therapeutic efficacy to aid in development of early treatments for Alzheimer’s disease,” Daggett stated.
Other experts say that even though more research is needed, the test presents an exciting step forward in preventing the disease and may encourage lifestyle changes to slow its progression.
The test presents an exciting step forward in preventing the disease and may encourage lifestyle changes to slow its progression.
“This may set the stage for the development of prevention strategies. With SOBA, the goal will be early detection to prevent the disease,” Raymond Tesi, MD, chief executive officer of INmuneBio, told Seasons.
For example, Tesi said if a patient takes the SOBA test and oligomers are found in their blood sample, clinical teams can search for risk factors of Alzheimer’s.
“Some risk factors can be modified by lifestyle changes – weight loss, control of hypertension and diabetes, and increased exercise,” Tesi said. “We have finally reached the point where two steps forward is two steps forward. The future is bright.”
We have finally reached the point where two steps forward is two steps forward. The future is bright.
Sullivan added that another significant point of the SOBA test is that it is aiming to be clinically available at the reasonable cost of an outpatient lab test and offered to real-world patients.
“Because oligomers happen so early in the AD process, the benefit would be early identification at a low cost,” she said.