Aptamers as Biomarkers for Neurological Disorders. Proof of Concept in Transgenic Mice
Blood-based diagnostics provide a minimally invasive way to detect molecular changes associated with disease. In this study, we used aptamers as biomarkers to profile blood serum and create diagnostic fingerprints for disease-related effects in a tauopathy mouse model.
Summary
We generated a deep library of oligonucleotide sequences by selecting aptamers against blood serum. We performed positive selection using pooled serum from transgenic P301S mice carrying the human tau gene and counter-selected against serum from wild-type mice. Next-generation sequencing (NGS) showed that many aptamer sequences remained consistent between selection rounds 5 and 6.
Next, we applied aliquots of the round 5 enriched library to serum from 16 individual mice for a single selection round. We used NGS to track changes in aptamer frequency between transgenic and wild-type mice. These differences allowed us to construct a diagnostic fingerprint, capturing the effect of the transgene on blood serum composition.
Our study demonstrates that aptamers can serve as effective biomarkers for detecting disease-associated molecular changes in blood. This approach provides a model for translating aptamer-based diagnostics to human subjects, enabling sensitive, personalized blood-based diagnostics.