“Currently, neuroimaging is required to diagnose Alzheimer’s disease,” said lead author Thomas Karikari, Ph.D., assistant professor of psychiatry at Pitt. “These tests are expensive and take a long time to schedule, and many patients, even in the United States, do not have access to MRI and PET scanners. Accessibility is a key issue.”
Clinicians currently use guidelines created by the National Institute on Aging and the Alzheimer’s Association in 2011 to diagnose Alzheimer’s disease. The AT(N) Framework requires detection by imaging or CSF analysis of the presence of three distinct components of Alzheimer’s pathology—amyloid plaques, tau tangles, and neurodegeneration in the brain.
Unfortunately, both procedures have economic and practical limitations, which require the development of simple and reliable AT(N) biomarkers in blood samples, the collection of which is minimally invasive and requires fewer resources. Developing basic methods for diagnosing Alzheimer’s disease in blood without compromising quality is an important step toward greater accessibility, according to Karikari.
“The most important benefit of blood biomarkers is to improve people’s lives and increase clinical confidence and risk prediction in the diagnosis of Alzheimer’s disease,” Karikari said.
Limitations of Currently Available Alzheimer’s Disease Detection Tests
Current blood testing techniques can detect abnormalities in the phosphorylated form of plasma amyloid beta and tau that meet two of the three criteria for a confident diagnosis of Alzheimer’s disease. The most challenging challenge in applying the AT(N) Framework to blood samples is to detect neurodegenerative markers that are specific to the brain and are not affected by potentially confounding contaminants produced elsewhere in the body.
For example, blood levels of neurofilament light, a protein marker of nerve cell destruction, are elevated in Alzheimer’s disease, Parkinson’s disease and other dementias, making it less effective in differentiating Alzheimer’s from other neurodegenerative diseases. On the other hand, detection of total tau in blood has been found to be less informative than monitoring its level in CSF.
Karikari and his team, which also included scientists from the University of Gothenburg in Sweden, applied their knowledge of molecular biology and biochemistry to develop a technique to detect BD-tau by avoiding free-floating “big tau” proteins produced by cells outside the brain. tau proteins in various tissues such as brain.
Monitoring BD-tau blood levels for the diagnosis of Alzheimer’s disease
To achieve this, scientists have created a unique antibody that prefers BD-tau and can easily detect it in the blood. They validated their analysis on more than 600 patient samples from five separate cohorts, including patients with a posthumous diagnosis of Alzheimer’s disease as well as patients with early-stage Alzheimer’s disease.
The experiments showed that levels of BD-tau found in blood samples from Alzheimer’s patients matched tau levels in CSF using the new assay and reliably distinguished Alzheimer’s from other neurodegenerative diseases. BD-tau levels were also found to correlate with the extent of amyloid plaques and tau tangles in brain tissue, as confirmed by autopsy analysis.
The scientists expect that monitoring BD-tau blood levels will improve clinical trial design and allow screening and recruitment of patients from populations traditionally excluded from research cohorts.
“There is a great need for diversity in clinical research, not just based on skin color, but also based on socioeconomic status,” Karikari said. “To develop better drugs, trials need to involve people from diverse backgrounds, not just those who live near academic medical centers. The blood test is cheaper, safer, and easier to administer, and it may increase clinical confidence in the diagnosis and selection of Alzheimer’s disease. participants for monitoring.”
Karikari and colleagues plan to conduct a large-scale clinical validation of blood BD-tau at a variety of research institutions, including those recruiting people of different racial and ethnic backgrounds, memory clinics, and the community. In addition, both elderly people without biological signs of Alzheimer’s disease and those at different stages of the disease will participate in these trials. These efforts will pave the way for BD-tau to be commercially available for widespread clinical and prognostic use and ensure that biomarker results are generalizable to people of all backgrounds.