Biomarkers

Alzheimers Dement. 2025 Dec;21 Suppl 2:e106925. doi: 10.1002/alz70856_106925.

ABSTRACT

BACKGROUND: Conventional blood sampling for the testing of Alzheimer's disease (AD) biomarkers depends on stringent, time-sensitive, and temperature-dependent protocols for processing, shipping, and storage. Dry plasma spots (DPS) present a simpler, more scalable alternative for the collection, storage, and transport of blood samples and may offer an alternative sampling when access to blood volume is limited. Notably, neurodegenerative biomarkers such as p-tau, NfL, and GFAP from DPS have demonstrated a strong correlation with paired plasma on other platforms. In this pilot study, we aimed to expand on these findings by exploring a broader panel of central nervous system (CNS) biomarkers using DPS, assessing their potential for reliable and accurate detection.

METHOD: We used the NULISA™ platform to test multiplex detection of a CNS biomarker panel (127 proteins) in DPS and matched plasma, examining plasma-DPS correlations. A discovery cohort (n = 14; mean age 71.1 ± 12.8 years; 8 females [57%]) was selected from the Clinical Neurochemistry Laboratory in Mölndal, Sweden. DPS (Telimmune™ Plasma Separation Card) spiked with venous blood, were analysed with their paired EDTA plasma collected by traditional venipuncture. Pearson correlation was used to compare protein quantification across sample types.

RESULT: We demonstrated several biomarker associations between DPS and plasma with a correlation coefficient >0.99 and p <0.0001 (Figure 1), including APOe4 (r = 0.996), IL6 (r = 0.995), and FABP3 (r = 0.994). Notably, AD-related biomarkers like p-tau181 (r=0.89), p-tau231 (r=0.86), GFAP (r=0.8), NPTX2 (r=0.92), NFL (r=0.95), SMOC1 (r=0.91), and total Tau (r=0.93) all showed strong correlations and p <0.0001. DOPA decarboxylase, relevant for LBD and atypical Parkinsonian disorders, also correlated strongly (r=0.98, p <0.0001). VGF, a biomarker of synaptic plasticity altered in AD and Major Depressive Disorder showed a strong correlation (r = 0.95, p <0.0001). Among 16 interleukins, 11 had r>0.8 (p <0.0003) and 4 had r>0.5 (p <0.05), with IL6 (r=0.995) and IL12 (r=0.994) correlating notably strong (p <0.0001). However, 25% of proteins have a weak correlation coefficient of r<0.5 with plasma.

CONCLUSION: Our findings highlight the potential of DPS as a practical and scalable tool for multiplex biomarker detection. Further research is required to identify and validate optimal AD biomarkers in DPS-based multiplex assays.

PMID:41520321 | DOI:10.1002/alz70856_106925