Innovative Biomarker Analytics for Brain Health: A Path to Early Detection and Intervention

The PPS I-Brain was a collaboration between three partners with the aim to explore whether specific biomolecules that can be measured in blood, and that change due to aging or disease, can serve as biomarkers for organ health, particularly brain health. 

Aging and neurodegenerative diseases, such as Alzheimer's, pose significant societal and economic challenges, affecting over 50 million people worldwide. Innovations in early diagnosis and monitoring are crucial to mitigate these impacts, potentially improving patient outcomes and reducing healthcare costs. 

This project used biobanked samples from aged and neurodegenerative mouse models, including brain and liver tissues, as well as plasma samples, to set-up robust assays and to identify and validate blood-based biomarkers. These findings were compared to human samples to develop non-invasive measures of brain health. The approach included sample collection and preparation, biomarker definition and assay development, validation and analysis, and data reporting and interpretation. 

In only 3.5 months, molecular signatures indicative of aging and neurodegeneration were first identified using a combination of literature studies, public databases, and partner expertise. For mouse plasma and organ samples eleven robust assay protocols were newly established and for human plasma samples 18 assays. All done with special attention to minimize disturbing matrix effects (in particular with organ homogenates) to enhance accuracy of the assay systems. Tissues were sourced from biobanks and prepared for biomarker analysis. The use of preclinical and human samples allowed optimal validation of the assays, resulting in solid methods that generated reproducible biochemical results. The project delivered insightful information about biomarker and protein expression differences within tissues and even between brain regions (e.g. hippocampus, thalamus, cortex). Further research is required, also with more samples, to analyze whether the biomarkers in plasma correlate with the histological measurements in certain brain areas or MRI data and are representative for brain health.