NEW YORK – Data presented by University of Gothenburg researchers at the Alzheimer's Association International Conference (AAIC) annual meeting this month suggests that finger prick blood samples could be suitable for measuring several important protein biomarkers linked to Alzheimer's disease.
According to Hanna Huber, a postdoctoral researcher at Gothenburg who helped conduct the project, the ability to use finger prick samples could "greatly increase the utility of blood biomarkers" for applications like screening for Alzheimer's, as well as for monitoring disease progression and response to treatment.
To date, Alzheimer's testing has largely relied on PET imaging or cerebrospinal fluid-based assays. These approaches have downsides, however. PET is expensive and difficult to scale. CSF testing, meanwhile, requires a lumbar puncture, a relatively invasive procedure that some individuals are reluctant to undergo, especially if they are asymptomatic.
These drawbacks have made blood-based testing a particularly hot area within Alzheimer's, with a number of companies, large and small, moving into the space. Recent US Food and Drug Administration approvals of Biogen's Alzheimer's drug Aduhelm (aducanumab) and Eisai's Alzheimer's drug Leqembi (lecanemab) have also driven interest, as physicians will need tests to identify patients who may benefit from these and/or future treatments.
Finger prick blood samples could be even more convenient than those taken by traditional phlebotomy, Huber noted, allowing, for instance, for the collection of samples in remote settings without the help of trained medical personnel. This, she added, could "greatly increase the number of participants in large-scale population-based studies."
The finger prick sampling study was led by Nicholas Ashton, associate professor of neurochemistry at the University of Gothenburg. In the study, the researchers collected dried-blood spots of both venous and finger prick blood from 77 patients of the ACE Alzheimer's Center in Barcelona. They then shipped the blood spots overnight to Gothenburg at ambient temperatures and measured the Alzheimer's biomarkers neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau (pTau 181 and pTau 217) in both sample types.
They found that in the venous blood spots the measurements of all four markers corresponded well with measurements in standard blood samples, while in the finger prick samples NfL, GFAP, and pTau 217 correlated well with standard samples, while pTau 181 did not.
Studies have indicated that different Alzheimer's markers will prove more or less useful for different applications. For instance, recent work by researchers at Gothenburg and Lund University found that plasma pTau 217 appears most useful for tracking Alzheimer's progression as opposed to early detection of the disease. GFAP also appeared linked to disease progression, but only weakly, and it did not provide additional information beyond that provided by pTau 217.
Other studies have indicated that adding plasma markers like GFAP and pTau 181 to plasma Aβ 42/40 ratio may be necessary to effectively identify patients with the amyloid pathology characteristic of Alzheimer's disease.
Huber said she and her colleagues tried to use finger prick samples to measure plasma Aβ 42/40 ratio, which is a component of Alzheimer's plasma tests from companies including C2N Diagnostics and Quest Diagnostics but found that while they were able to effectively measure Aβ 40, they could only detect Aβ 42 in about 30 percent of the samples.
"Since only the ratio of both amyloid proteins is a reliable biomarker, we didn't continue measuring Aβ 40 in the [finger prick] samples," she said.
The researchers used Quanterix's ultra-sensitive immunoassay platform for their measurements. Some studies have found that mass spectrometry-based approaches could offer more robust measurements of Aβ 42/40 ratio than immunoassays, but Huber said that because the effort was "a proof-of-concept study," the researchers "focused on developing the method with one technology."
While the Gothenburg team used traditional dried-blood spots in the project, a number of companies like Capitainer and Neoteryx have developed microsampling devices that could offer more streamlined and reproducible collection workflows.
Huber said the researchers are "evaluating a range of collection devices in order to find the best eligible device for an easy and convenient self-execute, remote sample collection."