Blood-based biomarkers are rapidly advancing Alzheimer’s disease (AD) research and diagnostics, enabling early detection and monitoring. However, traditional blood tests require venous draw, specialized labs, and strict handling protocols; barriers that limit widespread screening, especially in remote or resource-limited areas. 

A recent study from the University of Gothenburg, “Biomarkers of Alzheimer’s disease and neurodegeneration in dried blood spots—A new collection method for remote settings” published in Alzheimer’s & Dementia, highlights the promise of dried plasma spot (DPS) testing as a stable, precise, and accessible alternative for AD biomarker detection. 

Transforming Neurodegenerative Disease Testing with DBS/DPS 

Dried blood spot (DBS) and dried plasma spot (DPS) testing are micro-sampling techniques where small volumes of blood are collected on specialized filter paper or capillary devices. DPS devices typically employ an additional built-in technology that separates soluble proteins from cellular components. DBS/DPS eliminates the need for venipuncture and cold-chain logistics. While DBS/DPS have been widely used in newborn screening and infectious disease diagnostics, their application in neurology was previously limited due to the low abundance of biomarkers in blood. 

Now, ultrasensitive technologies like Simoa^® have made it possible to detect key neurological biomarkers in DBS/DPS samples. This study demonstrated that DPS measurements of p-Tau 181, p-Tau 217, Aβ40, Aβ42, NfL, and GFAP closely correlate with standard plasma testing and effectively distinguish amyloid-positive (A+) from amyloid-negative (A-) individuals-paving the way for broader adoption of DPS testing in AD research and clinical care. 

By enabling high-precision biomarker analysis without the constraints of traditional blood collection, DBS/DPS testing offers a scalable and equitable solution for early AD detection and disease monitoring worldwide. 

Analytical Approach for AD and Neurodegeneration Biomarkers 

Paired venous DPS and standard EDTA plasma samples were collected from a discovery cohort (n=154) and a validation cohort (n=115) of individuals with suspected AD. Simoa assays were used to measure a panel of biomarkers associated with AD pathology, neurodegeneration and neuroinflammation, including p-Tau 181, p-Tau 217, amyloid beta (Aβ40 and Aβ42), NfL, and GFAP. 

The researchers investigated the correlations of the paired measurements in DPS and EDTA plasma, and the power of DPS-biomarkers in distinguishing amyloid status as defined by CSF Aβ42/40 ratio measured by an independent platform.  

Study Highlights: 

Optimal sample extraction method is key to the success of DBS biomarker measurements 

The strongest correlation of the measurements of all tested biomarkers between the paired DPS and EDTA plasma samples was observed for DPS samples prepared in spin buckets without nylon membrane, as well as in protein precipitation plate. Interestingly, spotting blood volumes from 30 µL to 130 µL did not seem to be linearly correlated with the biomarker concentrations measured. 

Biomarkers are detectable in DPS, with variable stability overtime and at different storage conditions 

All tested biomarkers were detectable in DPS. Stability testing suggested that NfL, Aβ40, and Aβ42 were stable in DPS over the 6-month period tested at both room temperature and 4°C, while p-Tau 181 and GFAP concentrations appeared to drop over time, especially at higher storage temperature. 

Biomarker measurements in paired DPS and EDTA plasma are correlated, albeit with much lower concentrations in DPS 

For all measured analytes except for Aβ42/40, DPS and EDTA plasma values correlated significantly. The strongest correlations with EDTA plasma were found for NfL and GFAP followed by Aβ42, p-tau217, p-tau181, and Aβ40. In general, the concentrations obtained from DPS are significantly lower than their counterparts in EDTA plasma. 

DPS biomarkers show good diagnostic accuracy, equivalent to EDTA plasma, in discriminating amyloid positive (A+) from negative (A-) 

Within a subset of the validation cohort that had CSF biomarker data to determine amyloid positivity, the study found a significant correlation between three individual DPS markers (p-Tau 217, p-Tau 181, and GFAP) and amyloid status. In single-marker model, DPS p-Tau 217 demonstrated the highest accuracy in discriminating A+ from A- with an AUC of 0.87 (95% CI 0.76-1.00), followed by p-Tau 181 and GFAP. Overall, accuracies of DPS and EDTA biomarkers were equivalent in distinguishing A+ from A- individuals. 

DPS biomarkers correlate with cognitive status 

DPS GFAP, NfL, p-Tau 217 and p-Tau 181 showed a modest yet significant association with cognitive status defined by the Clinical Dementia Rating Scale (CDR) and Mini-Mental State Examination (MMSE), with strongest correlation found for p-Tau 217. 

Enabling Broader AD Screening and Global Research Access 

The findings of this study have significant implications for global AD research and clinical practice. DBS/DPS sampling offers a practical solution for: 

• Remote and underserved populations: Enabling sample collection in areas where access to specialized clinics or phlebotomy services is limited. 

• Longitudinal studies: Facilitating longitudinal sampling in large cohorts without the logistical challenges of venous blood draws. 

• Home-based monitoring: Allowing patients and caregivers to collect samples conveniently, reducing the burden on healthcare systems. 

By integrating Simoa technology with DBS sampling, researchers and clinicians can enhance early detection efforts by extending testing to wider populations and geographic regions, track disease progression by recurrent testing, and accelerate the development of disease-modifying therapies by broadening access to ideal trial candidates. 

Advancing Biomarker Research for Neurological Disorders through Innovative Sample Collection Methods 

This study reinforces the growing potential of blood-based biomarker testing in neurodegenerative diseases and highlights the role of DBS/DPS as a game-changing approach for increasing accessibility. As research continues to refine and validate DBS/DPS-based biomarker detection, this method may become a cornerstone of future diagnostics of AD and other neurological disorders, making early detection and monitoring more feasible on a global scale. To learn more about recent development of DBS/DPS applications in neurological disease testing, download our DBS/DPS Application Note. 

Quanterix remains committed to driving innovation in neurological disease research, providing ultrasensitive biomarker detection solutions that push the boundaries of what’s possible in precision medicine. To learn more about our neurological biomarker assays and how they support groundbreaking research, download our Brain Health Brochure. 

To support DBS/DPS biomarker testing Quanterix has recently released its Simoa^® Dry Blood Extraction kit, providing a simple, standardized, and Simoa-compatible protein extraction solution to streamline the DBS biomarker workflow for neurological disorders. 

Reference: 
Huber H, Blennow K, Zetterberg, et al. Biomarkers of Alzheimer’s disease and neurodegeneration in dried blood spots—A new collection method for remote settings. Alzheimer’s & Dementia. 2024 Apr;20(4):2340-52.