Scientists validate new laboratory testing platform for Alzheimer’s disease blood biomarkers

Scientists at the University of Pittsburgh have independently validated a new blood testing platform capable of simultaneously measuring more than a hundred Alzheimer’s disease biomarkers. The platform could improve clinicians’ ability to grasp the multifaceted nature of Alzheimer’s pathology and streamline early diagnoses of the disease. The report is published in Molecular neurodegeneration.

“Alzheimer’s disease should not be viewed from just one perspective,” said lead 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 the onset of cognitive symptoms.”

Early detection of pathological changes associated with Alzheimer’s disease, including signs of neuroinflammation and dysfunction of brain blood vessel function and communication between nerve cells, is essential to improve the effectiveness of newly developed infusion treatments. developed and to stop or slow the progression of the disease.

Capturing a detailed snapshot of molecular changes in the brains of people at risk for Alzheimer’s disease who are not yet experiencing cognitive or memory changes would allow scientists to track disease progression over time and, potentially, develop guidelines for early intervention.

However, the current system for diagnosing Alzheimer’s disease is imperfect: it requires a lot of resources and time, both for doctors and laboratory technicians, and can be tedious for patients, who must undergo repeated 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 of southwestern Pennsylvania.

All samples were sent for analysis to Alamar Biosciences, the manufacturer of a new blood biomarker analysis panel called the NULISAseq CNS Disease 120 Panel. In addition to measuring classic blood biomarkers of Alzheimer’s disease, including phosphorylated forms of tau, beta-amyloid, the neuroinflammation marker GFAP, and the 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 suite of conventional Alzheimer’s disease biomarker tests for each individual sample. Changes in biomarker profiles over two years were also compared to imaging-based measures of amyloid, tau, and neurodegeneration.

According to Karikari’s assessment, the NULISAseq panel detected several biomarkers correlated with patients’ amyloid positivity status and changes in amyloid burden over time. These biomarkers were all previously linked to Alzheimer’s disease, but most only when measured in cerebrospinal fluid, and included 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 asymptomatic people and 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 determine disease stage and predict disease progression, both of which are used for decision-making regarding clinical management and treatment plans.