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The Science Behind Your CerebralScoreTM Test

Understanding how we use cell-free DNA (cfDNA) and DNA methylation to provide insights into your cognitive wellness. Plain-English explanations backed by peer-reviewed research.

Science Basics

What is Cell-Free DNA (cfDNA)?

Every day, your cells naturally shed tiny fragments of DNA into your blood and saliva—similar to how skin sheds dead cells. These fragments are called cell-free DNA (cfDNA), and they carry information about cellular processes and aging.[1]

cfDNA has enabled noninvasive testing in areas like prenatal screening, cancer detection, and organ transplant monitoring. Those same principles are being explored for brain and cognitive wellness contexts.[1]

Understanding DNA Methylation

Methyl groups attach to DNA at CpG sites—modulating gene activity. Tissues and cell types maintain characteristic methylation patterns to regulate gene expression. These DNA methylation patterns which are found on cfDNA fragments also work like a postal return address for the fragment telling us from which cell or tissue it originated.[2,3] Brain regions can also show distinct methylation signatures, relevant to patterns observed across different neurodegenerative conditions.[4]

cfDNA and the Brain

The blood–brain barrier in normal and healthy states limits brain-derived materials in circulation. However, during neurodegeneration or injury, barrier integrity can change and neuron-derived, brain-region specific methylated cfDNA may appear in blood or saliva, enabling liquid-biopsy approaches that assess for the brain-derived cfDNA.[4,5]

How We Use It

From Your Saliva to Your CerebralScoreTM

Here’s the high-level process:

Step 1: Lab Analysis

Your saliva sample is processed in a CLIA-certified lab to isolate and read methylation patterns from cfDNA fragments in the saliva.

Step 2: Focused Analysis

We summarize methylation patterns across a research-informed panel of 209 genomic methylation markers to provide a biological signal.

Step 3: Your CerebralScoreTM

We generate your CerebralScoreTM by inputting the biological methylation signal to our AI model. The AI model, which has been trained on saliva cfDNA methylation data from healthy and unhealthy brain samples, determines how similar your saliva cfDNA methylation signal is to the healthy-brain reference database.

Important to Know

CerebralScoreTM is a wellness metric for longitudinal tracking. It is not diagnostic and is not intended to detect or treat disease. Discuss health questions with a qualified clinician.

Key Scientific References

  1. Annual Review of Biomedical Engineering (2024) — “Liquid Biopsy Based on Cell-Free DNA and RNA” — https://www.annualreviews.org/content/journals/10.1146/annurev-bioeng-110222-111259
  2. Moss et al., Nature Communications (2018) — “Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease” — https://www.nature.com/articles/s41467-018-07466-6
  3. Nature Communications (2024) — “A cfDNA methylation-based tissue-of-origin classifier for cancers of unknown primary” — https://www.nature.com/articles/s41467-024-47195-7
  4. Future Medicine (2022) — “Cell-free DNA methylation as a potential biomarker in brain disorders” — https://pmc.ncbi.nlm.nih.gov/articles/PMC9066291/
  5. Mavroudis et al., Diagnostics (2023) — “Review on the Role of Salivary Biomarkers in the Diagnosis of Mild Traumatic Brain Injury” — https://www.mdpi.com/2075-4418/13/9/1522