Scientists at the University of Pittsburgh have independently validated a new blood testing platform that can simultaneously measure more than a hundred biomarkers of Alzheimer’s disease. The platform could improve physicians’ ability to capture the multifaceted nature of Alzheimer’s disease and streamline early disease diagnosis. The report was published in Molecular neurodegeneration Today.
Alzheimer’s disease should not be viewed through a single lens. Capturing aspects of Alzheimer’s pathology in a panel of clinically validated biomarkers would increase the chance that the disease can be stopped before cognitive symptoms emerge.”
Thomas Karikari, Ph.D., M.Sc., sfirst author, assistant professor of psychiatry at Pitt
Early detection of pathological changes associated with Alzheimer’s disease, including signs of neuroinflammation and dysfunction of cerebral blood vessel function and nerve cell communication, is critical for improving the effectiveness of newly developed infusion treatments and for stopping or slowing the disease progression.
Capturing a detailed snapshot of molecular changes in the brains of individuals at risk for Alzheimer’s disease who are not yet experiencing cognitive or memory changes would allow scientists to monitor disease progression over time and ultimately provide guidelines for develop early intervention.
However, the current system for diagnosing Alzheimer’s disease is imperfect: it is labor-intensive and time-consuming for both physicians and laboratory technicians and can be burdensome for patients who undergo repeated invasive medical procedures.
For a proof-of-concept study, Karikari and his team tested blood samples from a cohort of 113 cohort-wise normal older adults living in an economically disadvantaged region of southwestern Pennsylvania.
All samples were sent for analysis to Alamar Biosciences, the manufacturer of a new blood biomarker analysis panel called “NULISAseq CNS Disease 120 Panel”. In addition to measuring classic Alzheimer’s blood biomarkers, including phosphorylated forms of tau, amyloid beta, neuroinflammation marker GFAP and nerve cell damage marker NEFL, the panel captures changes in approximately 120 other proteins linked to neurodegenerative diseases.
The performance of the NULISA platform was independently validated against a battery of tests of classical Alzheimer’s biomarkers for each individual sample. Changes in biomarker profiles over a two-year period were also compared with imaging-based measures of amyloid, tau and neurodegeneration.
According to Karikari’s assessment, the NULISAseq panel detected several biomarkers that correlated with patients’ amyloid positivity status and changes in amyloid burden over time. These biomarkers have all previously been linked to Alzheimer’s disease, but most only when measured in cerebrospinal fluid and include proteins associated with neuroinflammation, pathological changes in the cerebral vasculature and impaired communication between nerve cells.
Karikari hopes the platform can be used as a tool to track changes in blood biomarkers over time in individuals who are asymptomatic and in those already receiving treatment. His lab is developing a predictive model that correlates biomarker changes detected with NULISAseq with brain autopsy data and cognitive assessments collected over several years. Their goal is to identify blood biomarkers that can help stage the disease and predict disease progression, both used for decision-making around clinical management and treatment plans.
Other study authors include Xuemei Zeng, Ph.D., Tara Lafferty, MS, Anuradha Sehrawat, Ph.D., Yijun Chen, MS, Pamela Ferreira, Ph.D., Bruna Bellaver, Ph.D., Guilherme Povala , Ph.D., M. Ilyas Kamboh, Ph.D., William Klunk, MD, Ph.D., Ann Cohen, Ph.D., Oscar Lopez, MD, Milos Ikonomovic, MD, Tharick Pascoal, MD, Ph .D., Mary Ganguli, MD, MPH, Victor Villemagne, MD, and Beth Snitz, Ph.D., all of Pitt.
This research was supported by the National Institute on Aging (grants R01 AG083874, R37 AG023651, and R01 AG052521).
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Magazine reference:
Zeng, X., et al. (2024) Multi-analytical proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer’s disease. Molecular neurodegeneration. doi.org/10.1186/s13024-024-00753-5.