In order to identify a new sign of Alzheimer’s disease neurodegeneration in a blood sample, a team of neuroscientists led by a researcher from the University of Pittsburgh School of Medicine created a new test. Brain-derived tau, or BD-tau, is an improved biomarker over standard blood tests for detecting Alzheimer’s disease-related neurodegeneration in the clinic. It has a strong correlation with cerebrospinal fluid indicators of Alzheimer’s neurodegeneration and is Alzheimer’s disease-specific (CSF).
Clinicians now use 2011 criteria established by the National Institute on Aging and the Alzheimer’s Association to make a diagnosis of Alzheimer’s disease. The AT(N) Framework stipulates that imaging or analysis of cerebrospinal fluid (CSF) samples must reveal the presence of amyloid plaques, tau tangles, and neurodegeneration in the brain. Both methods have drawbacks in terms of cost and convenience, thus it is imperative that we find ways to detect AT(N) in blood samples that are less intrusive and more cost-effective.
An key step toward greater accessibility, according to Karikari, is the development of simple equipment capable of identifying symptoms of Alzheimer’s in the blood without sacrificing quality. It is possible to identify Alzheimer’s disease with a high degree of certainty using two of the three criteria now available in blood testing methods: anomalies in plasma amyloid beta and the phosphorylated form of tau.
Applying the AT(N) Framework to blood samples, however, is complicated by the fact that it is difficult to discover signs of neurodegeneration that are brain-specific and unaffected by potentially deceptive pollutants generated elsewhere in the body.
For instance, the protein marker of nerve cell destruction, neurofilament light, is raised in the blood in Alzheimer’s disease, Parkinson’s disease, and other dementias, making it less effective for distinguishing Alzheimer’s disease from other neurodegenerative disorders. However, measuring CSF tau levels was more illuminating than measuring blood tau levels.
We sought to address this challenge by generating an anti-tau antibody that selectively binds brain-derived tau and avoids the peripherally expressed ‘big tau’ isoform.
Karikari and his group, which included researchers from the University of Gothenburg, Sweden, used their understanding of the molecular biology and biochemistry of tau proteins in diverse tissues, such as the brain, to create a method to preferentially identify BD-tau while ignoring free-floating large tau proteins generated by cells outside of the brain.
They were able to achieve this by developing a specific antibody that binds to BD-tau, allowing for its detection in blood samples. Over 600 samples from patients with confirmed postmortem Alzheimer’s disease diagnoses and individuals with memory deficits suggestive of early-stage Alzheimer’s were used to verify their assay’s accuracy.
The results demonstrated that the novel assay accurately separated Alzheimer’s disease from other neurodegenerative illnesses by measuring BD-tau levels in blood samples from AD patients, which correlated with tau levels in CSF. Autopsy data indicated that a direct correlation existed between BD-tau levels and the extent to which amyloid plaques and tau tangles had developed in the brain tissue of the deceased.
Researchers believe that keeping an eye on patients’ BD-tau blood levels might help them better design clinical trials and incorporate previously underrepresented groups in their screening and recruitment efforts.
Clinical validation of blood BD-tau is planned on a broad scale by scientists across a variety of research organizations, including those that seek for volunteers from different racial and cultural origins, memory clinics, and the general public. In addition to people at various stages of Alzheimer’s disease, these trials will also involve healthy older persons.
These efforts are vital in ensuring that the findings from the biomarker are applicable to a broad range of individuals, and will pave the path for the commercialization of BD-tau for wider clinical and prognostic use.
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