- Finger-prick blood tests at home detected Alzheimer's biomarkers nearly as well as standard methods.
- The DROP-AD study suggested that dried blood spots could revolutionize screening approaches for clinical trials.
- Additional research and validation are required before this approach is ready for clinical use.
Measurements of phosphorylated tau 217 (p-tau217) in dried plasma spots (DPS) identified people with Alzheimer's disease nearly as well as venous blood, data from the DROP-AD project suggested.
Correlations between DPS p-tau217 and venous plasma p-tau217 were strong (rs=0.74, 95% CI 0.678-0.791, P<0.001) in adults from seven merged cohorts, reported Nicholas Ashton, PhD, of Banner Sun Health Research Institute in Sun City, Arizona, and colleagues.
DPS p-tau217 predicted cerebrospinal fluid (CSF) p-tau217 positivity, with an area under the curve of 0.863 (95% CI 0.809-0.917), the researchers wrote in Nature Medicine.
"In the future, if population-level screening is warranted or if treatment in asymptomatic populations is approved, dried blood spot sampling represents a viable approach to reach such populations rapidly and efficiently," Ashton told MedPage Today.
"Nevertheless, substantially more validation is required, including independent validation across cohorts and settings for this to be used," he emphasized.
Blood biomarkers like p-tau217 are emerging as a way to detect Alzheimer's disease. The first FDA-approved blood-based diagnostic test for Alzheimer's relies on measures of p-tau217 and beta-amyloid 1-42 concentrations in plasma.
Alzheimer's tests involving venipuncture are simpler and easier than lumbar punctures or PET imaging, but they have practical hurdles to overcome, including how blood samples are collected, handled, and stored. Dried blood spot (DBS) technology relies on finger-prick blood samples that can be collected at home and mailed to laboratories without refrigeration.
However, more work is needed before this approach is ready for clinical use, the researchers noted.
"The dried blood spot test is intended for research use only, specifically to facilitate inclusion of underrepresented study communities and to enable the collection of data from substantially larger cohorts than those examined in prior studies," Ashton said.
The DROP-AD project assessed the potential of DBS or DPS derived from capillary blood to detect Alzheimer's biomarkers in 337 participants from seven centers in Europe or the U.K. One center included people with Down syndrome, which is often considered to be a genetically determined form of Alzheimer's disease.
Overall, 304 participants had DPS or DBS and venous plasma samples. This included 252 participants who provided paired capillary DPS samples and venous plasma; this group had a mean age of 72.7 years and 56.7% were women.
While correlations between DPS p-tau217 concentrations and venous plasma samples were robust, the strength of these correlations varied by site.
"Importantly, p-tau217 levels showed a stepwise increase across clinical stages -- cognitively unimpaired, mild cognitive impairment, and Alzheimer's disease -- and demonstrated good accuracy in predicting CSF biomarker-confirmed Alzheimer's disease pathology," Ashton and co-authors pointed out.
"Notably, the method was also effective in individuals with Down syndrome, a population at high genetic risk for Alzheimer's disease but in whom standard blood sampling by venipuncture may be more complicated, revealing elevated biomarkers in those with dementia compared with asymptomatic individuals," they wrote.
The researchers also assessed unsupervised finger-prick blood collection and reported high concordance between supervised and self-collected samples.
Two other markers -- glial fibrillary acidic protein and neurofilament light (NfL) -- also tracked with venous plasma samples.
"Although our primary focus was on biomarkers of Alzheimer's disease neuropathology, the reliable detection of NfL from DPS samples has broader implications," Ashton and colleagues observed.
DBS tests may help studies of other disorders -- like frontotemporal dementia, atypical parkinsonian syndromes, multiple sclerosis, amyotrophic lateral sclerosis, and acute neurologic injuries -- where capillary NfL tracking could be valuable, they suggested.
Disclosures
This study was supported by open access funding provided by University of Gothenburg.
Ashton reported relationships with Alamar Biosciences, BioArctic, Biogen, Eli-Lilly, Neurogen Biomarking, Roche, Spear Bio, Quanterix, and Vigil Neurosciences.
Co-authors reported relationships with numerous pharmaceutical companies, nonprofit groups, government agencies, and other entities.
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