A new blood-based biomarker, brain-derived tau, can identify neurodegeneration specific to Alzheimer’s disease and differentiate it from other, related dementias, research indicates.
The novel biomarker outperformed current blood tests used to clinically diagnose Alzheimer’s related neurodegeneration, according to the findings reported in the journal Brain.
Brain-derived tau correlated well with biomarkers for Alzheimer’s neurodegeneration in cerebrospinal fluid, while offering a simpler means of assessment.
The findings could provide the missing piece of the puzzle in offering a full set of blood-based biomarkers for Alzheimer’s disease.
“At present, diagnosing Alzheimer’s disease requires neuroimaging,” said senior author Thomas Karikari, assistant professor of psychiatry at the University of Pittsburgh.
“Those tests are expensive and take a long time to schedule, and a lot of patients, even in the U.S., don’t have access to MRI and PET scanners. Accessibility is a major issue.”
Currently, Alzheimer’s disease is diagnosed in the U.S. according to the AT(N) guidelines set in 2011 by the National Institute on Aging and the Alzheimer’s Association.
This requires three components of Alzheimer’s pathology to be detected—amyloid plaques (A), tau tangles (T) and neurodegeneration (N) in the brain—and relies on established cerebrospinal fluid and neuroimaging biomarkers.
Blood-based biomarkers for amyloid-beta and phosphorylated (p)-tau have already been shown to have diagnostic accuracy and agree well with their corresponding cerebrospinal fluid and neuroimaging biomarkers.
However, the blood-based neurodegeneration marker neurofilament light (NfL) is not specific to Alzheimer’s disease.
Furthermore, blood total (t)-tau does not correlate well with cerebrospinal fluid t-tau, possibly because it mainly originates from peripheral, non-brain sources.
To address this, the researchers developed an immunoassay to selectively measure brain-derived tau in blood by using a monoclonal antibody engineered to specifically target tau isoforms originating in the brain.
They then examined the capabilities of the new biomarker in five independent research cohorts, comprising 609 participants in all.
The team showed brain-derived tau was specific to Alzheimer’s disease and was able to differentiate neurochemically defined Alzheimer’s disease from a biomarker-negative control group.
In addition, it was able to distinguish Alzheimer’s disease from other neurodegenerative diseases, including where there was neuropathological confirmation.
The novel biomarker was associated with the severity of plaque and tangle pathologies at autopsy, AT(N) biomarkers in cerebrospinal fluid, and cognition.
The researchers note: “The most well-validated blood biomarker for neurodegeneration, NfL, is unable to differentiate between Alzheimer’s disease and other dementias due to its increases in a wide range of neurodegenerative disorders.
“Consequently, the dementia research field currently lacks a blood biomarker that is specifically altered as a result of Alzheimer-type neurodegenerative changes, such as how plasma p-tau is to tau phosphorylation/pathology in the AT(N) framework.”
They add: “Our findings indicate that plasma [blood-derived]-tau might be a biomarker that is specific for Alzheimer’s disease-type neurodegeneration and can discriminate Alzheimer’s disease from other neurodegenerative diseases, as shown previously for [cerebrospinal fluid] t-tau.”