Biomarkers.

Background: The characterization of Alzheimer's disease (AD) and AD related dementias (ADRD) pathophysiology has been revolutionized by the development of highly sensitive blood-based biomarkers. Although blood-based biomarkers allow for greater access, cost effectiveness, and scalability, there are limitations for their implementation in resource-constrained low- and middle-income countries (LMICs) and rural settings, where access to equipment, freezers, and assays is often limited. Dried blood spot (DBS) collection emerges as a promising, convenient, and cost-effective method for acquiring blood samples in these contexts, but it is unclear whether highly sensitive assays typically applied to cerebrospinal fluid (CSF), plasma, or serum can detect biomarker concentrations accurately. This pilot study assessed the feasibility of using DBS to measure blood-based AD biomarkers by examining the agreement between ADRD biomarker concentrations derived from DBS and from plasma in older adults in rural South Africa.

Method: Data were collected from the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI), an ongoing population cohort of 5,059 adults aged ≥40 years living in Agincourt, South Africa. This study focuses on a sub-sample of 95 participants, whose venous blood and DBS were collected during the HAALSI visit and later tested for blood-based ADRD biomarkers, including neurofilament light chain (NfL), phosphorylated-tau181 (p-tau181), and glial fibrillary acidic protein (GFAP). Plasma and DBS markers were analyzed using commercially available Single molecule array assays (Quanterix) at the University of Gothenburg. We ran pairwise correlations that examined the association between the plasma and DBS measures of p-tau181, NfL, and GFAP.

Result: The sample consisted of 70.5% women, with an average age of 67.53 years (SD=9.69). We observed a positive correlation between plasma and DBS GFAP concentrations (r=0.78, p-value<0.001). However, DBS and plasma concentrations were not correlated for p-tau181 (r=0.05, p-value=0.62) or for NfL (r=-0.04, p-value=0.68).

Conclusion: These preliminary analyses suggest that GFAP concentration, a marker of astrogliosis, can be measured consistently in DBS. These findings have important implications for the selection and analysis of AD blood-based biomarkers in low-resource and LMIC settings, where venous blood draws may not be feasible.