For patients diagnosed with Alzheimer’s disease, irreversible damage from is estimated to begin 10 to 20 years before symptoms even present themselves. This is largely due to the accumulation of amyloid beta proteins that fold and clump together, or oligomers, in the hippocampus. Most cases of Alzheimer’s are only diagnosed after they exhibit symptoms such as memory loss, at which point the best treatments only slow further symptom progression. In the case of this debilitating disease, early detection and disease-modifying treatments are a must.
In order to improve the timeline from detection to treatment, University of Washington professor Valerie Daggett, PhD, and colleagues developed a new type of blood test, known by the acronym SOBA, that does just that. SOBA stands for soluble oligomer binding assay, and is able to detect and measure levels of oligomers in the blood of patients with Alzheimer’s disease. With their work published in the Proceedings of the National Academy of Sciences, they’ve opened up a new door for disease identification and treatment.
“What clinicians and researchers have wanted is a reliable diagnostic test for Alzheimer’s disease—and not just an assay that confirms a diagnosis of Alzheimer’s, but one that can also detect signs of the disease before cognitive impairment happens. 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,” said Dr. Daggett in an institutional press release. “What we show here is that SOBA may be the basis of such a test.”
SOBA detects α–sheet-containing toxic oligomers, such as amyloid β, which remain critical early players in the molecular pathology of Alzheimer’s and other amyloid diseases. Not only do designed α–sheet peptides inhibit toxic effects on neuronal signaling, but they also act as the capture agent for this assay. Essentially, the presence of α–sheet Aβ oligomers in blood plasma is associated with Alzheimer’s disease.
The investigators focused on 379 plasma samples from 310 study participants obtained from the University of Washington Alzheimer’s Disease Research Center biobank (Behavioral Neurosciences Group Sample and Data Repository). Individuals were classified based on a comprehensive clinical evaluation that placed them into diagnostic groups: non-cognitively impaired control (n = 221); mild cognitive impairment (n = 45); Alzheimer’s disease (n = 102); and other forms of cognitive impairment (n = 11).
SOBA detected amyloid β oligomers in patients with mild cognitive impairment and Alzheimer’s disease, as well as 10 controls who later progressed to mild cognitive impairment. This alone suggests that SOBA may provide standalone, preclinical detection of Alzheimer’s. Additionally, of 53 Alzheimer’s cases verified after death, 52 patients had blood samples containing toxic oligomers.
The anti-amyloid β antibody used on the plasma samples, SOBA-AD, was able to distinguish between Alzheimer’s and other forms of dementia. By using different detection antibodies, even non-Alzheimer’s forms of dementia could be diagnosed.
“As an example, we created SOBA-PD, which identified both active and preclinical Parkinson’s disease and Lewy body dementia cases, albeit the number of samples is small,” mentioned the investigators. “SOBA is not reliant on invasive sample collection procedures, multistep processing and enrichment, sophisticated proprietary equipment, patient information, advanced analytics with combinations of parameters to optimize discrimination, or inclusion of risk factors, making it potentially easy to deploy in standard labs and clinics.”
Like her peers, Dr. Daggett believes that this technology can go even further.
“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,” she concluded.
References:
- Valerie Daggett: UW bioengineering. UW Bioengineering | University of Washington Department of Bioengineering. (2022, September 14). Retrieved January 10, 2023, from https://bioe.uw.edu/portfolio-items/daggett/
- Shea, D., Colasurdo, E., Smith, A., Paschall, C., Jayadev, S., Keene, C. D., Galasko, D., Ko, A., Li, G., Peskind, E., & Daggett, V. (2022). Soba: Development and testing of a soluble oligomer binding assay for detection of amyloidogenic toxic oligomers. Proceedings of the National Academy of Sciences, 119(50). https://doi.org/10.1073/pnas.2213157119
- Urton, J. (2022, December 5). New blood test can detect ‘toxic’ protein years before alzheimer’s symptoms emerge, study shows. UW News. Retrieved January 10, 2023, from https://www.washington.edu/news/2022/12/05/alzheimers-blood-test/
- Alzheimer’s disease research center (ADRC), University of Washington. Alzheimer’s Disease Research Center. (n.d.). Retrieved January 10, 2023, from http://depts.washington.edu/mbwc/adrc
- Hopping, G., Kellock, J., Barnwal, R. P., Law, P., Bryers, J., Varani, G., Caughey, B., & Daggett, V. (2014). Designed α-sheet peptides inhibit amyloid formation by targeting toxic oligomers. eLife, 3, e01681. https://doi.org/10.7554/eLife.01681
- Home. AltPep. (2023, January 6). Retrieved January 10, 2023, from https://www.altpep.com/
- University of Washington. (2022, December 5). New blood test can detect ‘toxic’ protein years before Alzheimer’s symptoms emerge, study shows. ScienceDaily. Retrieved January 10, 2023 from www.sciencedaily.com/releases/2022/12/221205153722.htm