A self-administered, in-home, finger-stick blood test detected Alzheimer's disease (AD) biomarkers that correlated with cognitive performance in older adults — a finding that could open the door to large-scale dementia risk screening outside of clinical settings.
The cross-sectional observational validation study of 174 participants (mean age, 66 years; 54% female) showed capillary blood levels of p-tau217 correlated with episodic memory, attention, and executive function, while glial fibrillary acidic protein (GFAP) correlated with working memory and executive function, as measured by computerized cognitive tests.
When researchers combined the p-tau217 results with composite memory scores, they identified a high-risk group — about 9% of participants — who performed significantly worse across cognitive and functional measures.
The approach is designed to move AD biomarker testing out of specialist clinics and into the community, where most people with early cognitive concerns are never evaluated.
"This is the whole reason for doing the capillary blood sampling — to allow it to be scalable, to allow it to be done at a community level, which is where it's likely to be most usefully employed," study investigator Anne Corbett, PhD, professor in dementia research at the University of Exeter Medical School, Exeter, England, told Medscape Medical News.
The study was published online May 6 in Nature Communications.
Building on the DROP-AD Foundation
The study builds on the DROP-AD trial, which validated capillary blood sampling for AD biomarkers in 337 participants.
As reported previously by Medscape Medical News, that study demonstrated strong concordance between capillary and venous samples — but collection was still supervised in clinical settings. In the current study, participants collected samples entirely at home and returned them by mail.
In the UK, only 1 in 1000 people with early cognitive decline receive a specialist evaluation. Corbett said the study deliberately set its memory threshold at 1 SD below age-matched norms — milder than the 1.5 SD cutoff for mild cognitive impairment — to catch people earlier in the disease course.
"When you look at the new generation of disease-targeted treatments, they are looking for preclinical mild cognitive impairment with biomarkers," she said. "That's even more relevant in the US, where some of these drugs are already in use."
Participants were either cognitively normal (n = 146) or had mild to moderate dementia (n = 28). Each collected 70 μL of capillary blood using a Capitainer dried blood spot device. Cards were dried at room temperature and mailed without cooling.
Capillary p-tau217 correlated with episodic memory (r = 0.299; P < .001), attention (r = 0.197; P = .019), and executive function (r = 0.191; P = .021). GFAP correlated with working memory (r = 0.183; P = .034) and executive function (r = 0.182; P = .046).
Both biomarkers discriminated between participants with and without dementia, though with modest accuracy (p-tau217 AUC = 0.656, P = .012; GFAP AUC = 0.688, P < .001). The high-risk group identified through the dual-threshold approach showed large effect sizes across cognitive and functional domains (Cohen d > 1.0).
In a subgroup of 40 participants with paired venous samples, capillary-venous correlations were strong (p-tau217: r = 0.711-0.743; GFAP: r = 0.700-0.790).
An unexpected finding was that only 6% of participants were positive for both biomarkers. GFAP-positive participants were nearly five times more likely to report a history of heart disease (odds ratio, 4.14; P = .016), while p-tau217 positivity had no cardiovascular association, suggesting the two markers may identify distinct at-risk populations.
"We didn't expect quite such a separation," Corbett said. She described the finding as exploratory and said her group planned to examine whether the two groups showed different cognitive trajectories.
Corbett estimated a timeline of 4 to 5 years before the approach could enter clinical pathways and said her group was launching a study this summer to prototype the technology in a real-world NHS context.
Foundational Research
Commenting for Medscape Medical News, Suzanne Schindler, MD, PhD, associate professor of neurology at Washington University School of Medicine, St. Louis, Missouri, said the study addressed a real problem but that the data supported feasibility, not clinical readiness.
"This isn’t ready for clinical practice, but it's laying groundwork for future studies," Schindler said.
She noted the cohort lacked a dedicated mild cognitive impairment (MCI) group, making it difficult to assess the tool's effectiveness in a population it seemed designed to reach. "They likely will be able to identify some of the individuals at highest risk and lowest risk, but there's going to be a lot of people that aren't stratified," said Schindler, who was not involved in the study. "It has value for the extremes, but for those folks in the middle, it's not going to stratify them."
Schindler differentiated this approach from a previous direct-to-consumer blood biomarker test by Quest Diagnostics that drew criticism for high false-positive rates. That test used the amyloid-beta 42-to-40 ratio, which was less specific, and was framed as a clinical tool. The current study's higher-specificity cutoff and triaging framing made it less concerning, she said.
She noted that blood biomarker testing is recommended only for symptomatic individuals, in part because approved treatments target people who already have cognitive impairment. But trials are underway testing anti-amyloid therapies in people with no symptoms.
"If that happens, we will then have a need to screen people who are cognitively unimpaired," she said, a scenario that would make scalable, home-based testing far more urgent.
Marwan Sabbagh, MD, professor of neurology and Moreno Family Chair for Alzheimer's Research at the Barrow Neurological Institute, Phoenix, Arizona, who was also not involved in the research, said the sample needed to be much larger and more diverse. "You need a bigger spread. … You need more MCI," Sabbagh told Medscape Medical News.
But Sabbagh did see major potential in getting at-risk individuals into the clinical pathway more quickly than what’s traditionally done.
"A typical 70-year-old goes to primary care, and primary care may or may not screen them, may or may not evaluate them, and may or may not refer them," he said. Capillary testing could compress that timeline dramatically — flagging at-risk individuals through an online cognitive test, sending a kit in the mail, and returning a result in days rather than months.
He added that capillary testing could eventually replace venous plasma testing as a gating mechanism before PET scans, but he said the field was not ready for a direct-to-consumer model.
"This could become part of the annual Medicare wellness visit," Sabbagh said. "I'm not sure we're ready to jump to a direct-to-consumer model."
The study was funded by the National Institute for Health and Care Research Invention for Innovation program and the NIHR Exeter Biomedical Research Centre. Disclosure information for study authors is available in the original study publication. Schindler reported no relevant financial relationships.
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