Researchers from the United States have developed a new test to detect toxic amyloid β-peptide (Aβ) oligomers. They have reported the results of their study using the new test, called soluble oligomer binding assay or SOBA, in the Proceedings of the National Academy of Sciences.^1,2

To validate SOBA, they tested it on human plasma samples that had been obtained from 310 participants for research purposes. None of the participants had any signs of cognitive impairment, mild cognitive impairment, Alzheimer’s disease or other dementia at the time of sample collection.

The assay could detect Aβ oligomers in patients with mild cognitive impairment and moderate to severe Alzheimer’s disease. In 53 cases, the diagnosis of Alzheimer’s disease was confirmed on autopsy; 52 of these samples were positive for toxic oligomers using SOBA.

The toxic oligomers were also detected among 11 persons in the control group. A review of records showed that on follow-up, 10 of the 11 controls had developed mild cognitive impairment or Alzheimer’s. The remaining members of the control group, who did not have cognitive impairment, were negative for the toxic oligomers. SOBA also exhibited a sensitivity and specificity of 99% in differentiating Alzheimer’s disease from other types of dementia.

Researchers also showed that SOBA was amenable to modification to detect toxic oligomers of another type of protein associated with Parkinson’s disease and Lewy body dementia.2

“Toxic Aβ oligomers contain a nonstandard protein structure, termed α-sheet, and designed α–sheet peptides target this main-chain structure in toxic oligomers independent of sequence” write the authors.1 The attached oligomers can be tested for amyloid beta proteins using standard methods. “Pre-incubated synthetic α–sheet-containing Aβ oligomers produce strong SOBA signals, while monomeric and β-sheet protofibrillar Aβ do not”.

In what could be a breakthrough in the management of Alzheimer’s disease, which currently has no cure, these findings from the proof-of-concept study suggest that SOBA may be a reliable diagnostic test for Alzheimer’s disease. The striking advantage is that it can detect signs of the disease decades before the disease manifests in the form of cognitive impairment, when the disease is already in an advanced stage. Early detection allows early intervention.

References

1. Shea D, et al. SOBA: Development and testing of a soluble oligomer binding assay for detection of amyloidogenic toxic oligomers. Proc Natl Acad Sci U S A. 2022 Dec 13;119(50):e2213157119. doi: 10.1073/pnas.2213157119.
2. https://www.washington.edu/news/2022/12/05/alzheimers-blood-test/, Dec. 5, 2022. Accessed on Jan. 14, 2023.