A team at the University of Pittsburgh has developed a novel blood test capable of measuring over 100 biomarkers associated with Alzheimer's disease. This new diagnostic approach could offer a less invasive alternative to traditional spinal taps for diagnosing the neurodegenerative condition, potentially streamlining early disease detection and management. The research, led by Thomas Karikari, PhD, Assistant Professor of Psychiatry at the University of Pittsburgh, was published in Molecular Neurodegeneration.
Addressing Limitations in Alzheimer's Diagnostics
Traditional methods of detecting Alzheimer's disease often rely on the analysis of cerebrospinal fluid (CSF) obtained through lumbar punctures. While blood-based biomarkers like phosphorylated tau protein (pTau) have emerged as possibilities, significant obstacles remain. According to Karikari and his team, these include the lack of methods for multi-analyte assessments and the need for biomarkers reflecting related pathophysiological processes such as neuroinflammation, vascular, and synaptic dysfunction.
The NULISAseq CNS Disease Panel
To overcome these limitations, the researchers utilized the NULISAseq CNS Disease Panel 120 by Alamar Biosciences. This panel allows for the simultaneous analysis of 120 neuro-specific and inflammatory proteins from a small sample of plasma or CSF. It detects critical biomarkers, including pTau-217, glial fibrillary acidic protein (GFAP), neurofilament light polypeptide (NEFL), and alpha-synuclein.
The study involved analyzing 176 blood samples from 113 adults with an average age of 76.7 years. The NULISAseq platform's performance was validated against conventional assays for classic Alzheimer's biomarkers. Furthermore, biomarker profiles over two years were compared with imaging-based measures of amyloid, tau, and neurodegeneration.
Key Findings and Implications
The results demonstrated the test's ability to detect biomarkers correlating with patients' amyloid positivity status and changes in amyloid burden over time. Notably, the test also identified biomarkers related to neuroinflammation, synaptic function, and vascular health, which had not previously been validated in blood samples.
"Alzheimer’s disease should not be looked at through one single lens," said Karikari. "Capturing aspects of Alzheimer’s pathology in a panel of clinically validated biomarkers would increase the likelihood of stopping the disease before any cognitive symptoms emerge."
Future Directions
Karikari envisions this diagnostic platform being used to track individuals' blood biomarker changes over time. His lab is currently developing a predictive model that correlates biomarker changes detected using NULISAseq with brain autopsy data and cognitive assessments collected over several years. The goal is to identify blood biomarkers that can help stage the disease and predict its progression, aiding in clinical management and treatment planning.
With approximately seven million Americans currently affected by Alzheimer's disease and projections estimating a rise to 13 million by 2050, the development of more accessible and comprehensive diagnostic tools is crucial. This research, supported by the National Institute on Aging, represents a significant step towards improving early detection and personalized management of Alzheimer's disease.
