A Finger-Prick Test for Alzheimer’s Disease?

Series - Alzheimer's Association International Conference (AAIC) 2024:

Jab a finger, draw up a spot of blood with a test strip, let it dry, then mail it off to your doctor. Could testing for Alzheimer’s disease become that simple? Quite possibly. Modern immunoassays are so sensitive they can detect markers in that way.

  • Ultra-sensitive immunoassays detect markers in a drop of blood.
  • The drop can be separated into plasma and dried for later analysis.
  • P-tau isoforms, GFAP, NfL can be measured.

At AAIC 2024, held last month in Philadelphia, Nicholas Ashton, Banner Alzheimer’s Institute, Phoenix, reported that p-tau217 is one such protein. Measuring this tau fragment in dried plasma spots identified people with Alzheimer’s disease about as well as did using venous blood, Ashton showed.

Henrik Zetterberg, University of Gothenburg, Sweden, works with Ashton on a project called Drop-AD to evaluate this methodology. He said it can measure other markers as well. Sebastian Palmqvist, University of Lund, Sweden, told Alzforum that the finger-prick analysis could be hugely helpful in countries where there are large rural populations with limited access to centrifuges needed to process venous blood draws.

For now, one dried spot is needed to test each marker, but new technology coming down the pike can measure more than 100 from a single finger prick. Called NULISA, it uses proximity ligation of nucleic-acid-tagged antibodies to amplify signals in biofluids in multiplex analysis. It is catching on in multiple labs (see next story).

Drop-AD
At AAIC, Ashton and Hanna Huber, University of Gothenburg, presented how their project analyzed blood from 327 volunteers at five centers across Europe and one in the United States. Of these, 165 were tested for amyloid pathology and 289 for tau pathology using previously established cutoffs in venous blood for the Aβ42/40 ratio and p-tau217, respectively. Each person also had a finger pricked to draw a few dozen microliters of capillary blood into test strips that either dried the blood as is, or separated out the red blood cells first, since protein markers are generally more stable in plasma.

Scientists at the various centers then shipped the cards, at ambient temperature, to Gothenburg, where Huber measured p-tau217 in the dried spots using the commercially available ALZpath immunoassay.

Drop It! Some microliters of blood from a finger prick contain enough p-tau217 to be measured on commercial immunoassay platforms. [Image courtesy Nick Ashton.]

At AAIC, Ashton showed that the concentrations of p-tau217 in capillary blood, as measured on the dried spots, were about 40-fold lower than in venous blood. That was not a big problem, though, because the two correlated tightly. Importantly, dried blood spot (DBS) p-tau217 identified people with amyloid pathology with a specificity and sensitivity that almost equaled that of venous p-tau217. Huber showed that the DBS assay distinguished amyloid-positive and p-tau217-positive people from their respective controls.

All told, the data indicate that it may well become possible to use such a simple finger-prick sampling approach for in-home testing. Much work remains. The method has to be tested in other cohorts, and in real-world settings, as these samples were taken in research clinics. “We need to see how these tests perform when people collect their own samples unsupervised,” Ashton said.

Zetterberg told Alzforum that the dried blood spots already work well for p-tau181, p-tau231, GFAP, and NfL. “We can measure these with excellent correlation with venous blood levels,” he said (Huber et al., 2024; Kolanko et al., 2024). 

One downside? Each test strip can only be used once to measure one marker. Hence no multiplexing. Here’s where NULISA can help. This new type of assay can measure more than 100 central nervous system proteins simultaneously—in one dried plasma spot, and with sensitivities 10- to 20-fold higher than single molecule array (SIMOA) immunoassays currently used to measure AD markers (see next story).—Tom Fagan

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References

News Citations

  1. NULISA—A New Proteomic Method to Revamp Biomarker Analysis

Paper Citations

  1. Huber H, Blennow K, Zetterberg H, Boada M, Jeromin A, Weninger H, Nuñez-Llaves R, Aguilera N, Ramis M, Simrén J, Nilsson J, Lantero-Rodriguez J, Orellana A, García-Gutiérrez F, Morató X, Ashton NJ, Montoliu-Gaya L. Biomarkers of Alzheimer's disease and neurodegeneration in dried blood spots-A new collection method for remote settings. Alzheimers Dement. 2024 Apr;20(4):2340-2352. Epub 2024 Jan 29 PubMed.
  2. Kolanko MA, Huber H, David MC, Montoliu-Gaya L, Simrén J, Blennow K, Zetterberg H, Nilforooshan R, Malhotra P, Sharp DJ, Ashton NJ, Graham NS. Quantification of neurofilament light and glial fibrillary acidic protein in finger-prick blood. Brain Commun. 2024;6(3):fcae151. Epub 2024 Apr 29 PubMed.

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