A new clinical laboratory blood test developed by University of Pittsburgh scientists could revolutionize the diagnosis of Alzheimer's disease by measuring over 100 different genetic sequences associated with the condition. This innovative approach may offer a less invasive alternative to traditional spinal tap procedures, streamlining early disease diagnostics and capturing the multifaceted nature of Alzheimer's pathology.
The proof-of-concept study, published in Molecular Neurodegeneration, highlights the potential of this diagnostic platform to overcome limitations in current blood-based biomarker detection methods. According to Thomas Karikari, PhD, Assistant Professor of Psychiatry at the University of Pittsburgh and lead author of the study, the focus on classical Alzheimer's blood biomarkers has hindered the exploration of other pathophysiological processes like neuroinflammation, vascular, and synaptic dysfunction.
Multi-Analyte Assessment
The study addressed the need for multi-analyte assessments by utilizing the NULISAseq CNS Disease Panel 120, developed by Alamar Biosciences. This panel allows for the simultaneous analysis of 120 neuro-specific and inflammatory proteins from a small sample of plasma or cerebrospinal fluid (CSF). The test employs a proprietary sequential immunocomplex capture and release mechanism combined with next-generation sequencing technology.
The researchers analyzed 176 blood samples from 113 adults with an average age of 76.7 years. The NULISAseq platform enabled the detection of biomarkers correlating with patients' amyloid positivity status and changes in amyloid burden over time. It also identified biomarkers related to neuroinflammation, synaptic function, and vascular health, which had not previously been validated in blood samples.
Tracking Disease Progression
Karikari envisions the diagnostic platform being used to track individuals' blood biomarker changes over time. The study results included novel protein targets that provide information about the disease state of the individual in different pathological stages across the biological Alzheimer's disease continuum.
"Alzheimer’s disease should not be looked at through one single lens. 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," said Karikari.
Implications for Clinical Practice
With approximately seven million Americans currently affected by Alzheimer's disease, and projections estimating a rise to 13 million by 2050, the need for improved diagnostic tools is critical. This new blood test offers the potential for earlier and more comprehensive detection of Alzheimer's, which could lead to better clinical management and treatment plans.
Karikari's 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, both for decision-making around clinical management and treatment plans.
Further studies are planned with larger and more diverse samples to validate the findings and refine the predictive model. This research was supported by the National Institute on Aging.
