Could a Blood Test Detect Alzheimer’s Earlier?

One of the first stages of Alzheimer’s disease involves formation of toxic aggregates, called oligomers, of the protein amyloid beta (Aβ). Oligomers can start to form more than a decade before symptoms and other known disease markers appear. The ability to detect these oligomers could enable earlier diagnosis and the potential to intervene before irreparable brain damage occurs.

An NIH-funded team led by researchers at the University of Washington developed a method to detect toxic Aβ oligomers in patients’ blood. They tested the assay, called the soluble oligomer binding assay (SOBA), on nearly 400 banked human blood plasma samples. Results appeared in the Proceedings of the National Academy of Sciences.

When the team applied SOBA to a cerebrospinal fluid sample from a person with Alzheimer’s disease, they detected Aβ oligomers. They did not detect oligomers in cerebrospinal fluid from a person who had no cognitive impairment.

Next, the researchers tested whether SOBA could detect Aβ oligomers in blood samples. The samples came from more than 300 people. SOBA detected toxic oligomers in 52 of 53 people with Alzheimer’s disease or mild cognitive impairment. It did not detect oligomers in most of the control samples. 

Ten of these positive samples came from people who later developed mild cognitive impairment. This shows that the SOBA test detected the toxic Aβ oligomer before Alzheimer’s symptoms appeared. The team also measured conventional Alzheimer’s disease biomarkers in cerebrospinal fluid samples from the same people. None of these correlated with disease state as well as the SOBA method did.

SOBA distinguished Alzheimer’s disease from other forms of cognitive impairment. The team designed SOBA to detect only oligomers of Aβ and not of other proteins. Consistent with this, samples from people with other forms of cognitive impairment tested negative.

Other neurodegenerative diseases, such as Parkinson’s disease, also involve toxic protein oligomers. The team showed that SOBA could be modified to detect Parkinson’s disease and Lewy body dementia.

These results suggest that SOBA could detect toxic oligomers in the blood even before cognitive impairment occurs.—adapted from NIH Research Matters