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First Human Test Application of the Aptamarker Platform

admin — Mon, 04 Jan 2021 21:40:00 +0000

First Human Test Application of the Aptamarker Platform

The first human test of the Aptamarker Platform demonstrated its ability to screen plasma for all possible biomarkers simultaneously. This milestone was highlighted in the study “Aptamarker prediction of brain amyloid-β status in cognitively normal individuals at risk for alzheimer’s disease.” The paper showed how the platform can be used for the prediction of brain amyloid-β accumulation in at-risk, cognitively normal individuals, marking a significant step forward in early disease detection. By analyzing proteins directly in human plasma, the Aptamarker Platform revealed insights that traditional biomarker approaches might miss, underscoring its transformative potential in human diagnostics and biomarker discovery.

Aptamarker prediction of brain amyloid-B status in cognitively normal individuals at risk for Alzheimer's disease

In this study, researchers focused on predicting brain amyloid-β deposition using plasma samples. Brain amyloid-β plaques represent a key risk factor for Alzheimer’s disease. Researchers compared cognitively normal individuals over the age of 70. Participants differed in the level of brain amyloid detected through PET scans in the INSIGHT study group.

Researchers performed positive selection using plasma from individuals with high brain amyloid levels. They performed negative selection using plasma from individuals with low brain amyloid levels. This approach enriched the aptamer library for relevant molecular signals. Researchers then applied the selected library to plasma samples from 22 individuals. Eleven individuals had high brain amyloid levels, and eleven had low levels.

Researchers used next-generation sequencing to analyze each selected library and measure the frequency of 10,000 aptamer sequences. They then evaluated these sequences using sparse partial least squares discriminant analysis. This analysis aimed to identify sequences that explained variation in brain amyloid deposition.

The analysis identified a subset of 44 aptamers. Researchers synthesized these aptamers individually. They then applied the aptamer panel to plasma samples from 70 cognitively normal individuals over the age of 70. Fifty-four samples formed the training set, while fifteen samples formed the test set. The model misclassified three individuals in the test set. Overall, the model achieved 80% accuracy, with 86% sensitivity and 75% specificity.

These aptamers function directly as biomarkers. For this reason, researchers call them Aptamarkers.

The first human test application of the Aptamarker platform demonstrates a new path for biomarker discovery. Researchers can screen plasma broadly without relying on predefined targets. This approach may support earlier disease detection and deeper biological insights.

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Review Paper: Blood Based Diagnostics of Alzheimer’s Disease.

admin — Mon, 03 Jun 2019 21:16:00 +0000

Blood Based Diagnostics of Alzheimer's Disease.

Early detection of Alzheimer’s disease (AD) relies on identifying reliable biomarkers in blood. In our study, we focused on the methods of biomarker discovery rather than the biomarkers themselves. We aimed to examine how experimental design, phenotype contrasts, and analytical strategies influence discovery, while also introducing our Aptamarkers platform as a novel tool for identifying pathogenic epitopes specifically for a blood based diagnostics of Alzheimer’s Disease.

Summary

We show that all biomarker discovery programs fundamentally depend on contrasting phenotypes to detect meaningful differences. In our work, we explored how these contrasts vary based on biomarker type, including genetic markers, proteins, metabolites, non-coding RNA, and pathogenic epitopes. Using our Aptamarkers platform, we demonstrated the ability to identify pathogenic epitopes in an agnostic, non-hypothesis-driven manner, avoiding the constraints of pre-existing assumptions about disease mechanisms.

We highlight that limiting biomarker discovery to molecules already believed to play a role in AD pathophysiology imposes unnecessary constraints. By contrast, our approach uses complex contrasts and mathematical models to capture the multifactorial nature of Alzheimer’s disease, enabling the detection of novel biomarkers and patterns that traditional methods may miss.

Our study emphasizes that agnostic, data-driven biomarker discovery accelerates understanding of Alzheimer’s disease. By moving beyond hypothesis-based selection, researchers can uncover new, informative biomarkers. The Aptamarkers platform exemplifies how innovative technologies can enhance discovery, supporting earlier diagnosis and enabling more effective interventions.

The post Review Paper: Blood Based Diagnostics of Alzheimer’s Disease. appeared first on NeoVentures Biotechnology Europe.

Aptamers as Biomarkers for Neurological Disorders

admin — Fri, 05 Jan 2018 22:26:00 +0000

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.

The post Aptamers as Biomarkers for Neurological Disorders appeared first on NeoVentures Biotechnology Europe.