image: Thomas Karikari, Ph.D., M.Sc., assistant professor of psychiatry at the University of Pittsburgh
Credit: University of Pittsburgh
University of Pittsburgh scientists independently validated a new blood test platform that can simultaneously measure more than a hundred biomarkers of Alzheimer's disease. The platform might improve clinicians’ ability to capture the multifaceted nature of Alzheimer’s pathology and streamline early disease diagnostics. The report was published in Molecular Neurodegeneration today.
“Alzheimer’s disease should not be looked at through one single lens,” said senior author Thomas Karikari, Ph.D., M.Sc., assistant professor of psychiatry at Pitt. “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.”
Early detection of pathological changes associated with Alzheimer's disease, including signs of neuroinflammation and dysfunction in brain blood vessel function and nerve cell communication, is key to improving effectiveness of newly developed infusion treatments and to stopping or slowing down disease progression.
Capturing a detailed snapshot of molecular changes in the brains of individuals at risk of Alzheimer’s disease who are not yet experiencing any cognitive or memory changes would allow scientists to track disease progression over time and, eventually, develop guidelines for early intervention.
However, the current system for diagnosing Alzheimer’s disease is imperfect – it is resource-intensive and time-consuming for both physicians and lab technicians and can be burdensome for patients who must repeatedly undergo invasive medical procedures.
For a proof-of-concept study, Karikari and his team tested blood samples from a cohort of 113 cognitively normal older adults living in an economically underserved region in 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 classical 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 about 120 other proteins related to neurodegenerative diseases.
The performance of the NULISA platform was independently validated against a series of assays of classical Alzheimer’s biomarkers for each individual sample. Changes in biomarker profiles over two years 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. Those biomarkers were all previously linked to Alzheimer’s disease but most only when measured in the cerebrospinal fluid and included proteins associated with neuroinflammation, pathological changes in brain vasculature and impaired communication between nerve cells.
Karikari hopes that the platform could be used as a tool to keep track of blood biomarker changes over time in individuals who are asymptomatic and those who are 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 the course of 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 authors of the research are Xuemei Zeng, Ph.D., Tara Lafferty, M.S., Anuradha Sehrawat, Ph.D., Yijun Chen, M.S., Pamela Ferreira, Ph.D., Bruna Bellaver, Ph.D., Guilherme Povala, Ph.D., M. Ilyas Kamboh, Ph.D., William Klunk, M.D., Ph.D., Ann Cohen, Ph.D., Oscar Lopez, M.D., Milos Ikonomovic, M.D., Tharick Pascoal, M.D., Ph.D., Mary Ganguli, M.D., M.P.H., Victor Villemagne, M.D., 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).
Journal
Molecular Neurodegeneration
Article Title
Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer’s disease