Could better blood tests help detect Alzheimer’s early, before symptoms appear?
Kaj Blennow, M.D., Ph.D.
University of Gothenburg
Several emerging methods may allow detection of brain changes associated with Alzheimer’s in the blood and cerebrospinal fluid (CSF, the biological fluid surrounding the brain and spinal cord) long before symptoms appear. This requires measuring specific biological markers, or “biomarkers,” (such as the level of tau protein, which accumulates to form tau tangles, a hallmark brain change observed in Alzheimer’s) from the biological samples.
Tau is normally modified by the addition of a molecule known as phosphate to specific parts of the tau protein. In Alzheimer’s and other brain diseases, tau becomes excessively phosphorylated (high levels of phosphate added to the tau protein) and then clumps together to form tangles. These tangles have been shown to cause brain cell damage and death. Brain diseases believed to result from abnormal modification of the tau protein are referred to as “tauopathies”.
There are many forms of phosphorylated tau (or “pTau”) including pTau181, pTau217, and pTau231, which differ by the location on the tau protein where the phosphate molecule is added. Past studies by Dr. Kaj Blennow and colleagues have shown that blood and CSF samples from people with Alzheimer’s may contain many different forms of pTau. Preliminary results from Dr. Blennow’s team show that in particular, pTau231 may be found in blood samples from individuals with early Alzheimer’s. Dr. Blennow and colleagues will study whether certain forms of pTau correspond to different stages of disease.
Building on their preliminary results, Dr. Blennow and colleagues will study several different approaches to detect pTau in blood and CSF samples. To do so, the researchers will leverage several ongoing long-term studies in Canada and Europe that have collected blood and CSF samples from older cognitively unimpaired individuals and those with abnormal tau-related brain diseases including Alzheimer’s.
The researchers will expose the CSF and blood samples to different combinations of antibodies that can specifically detect each form of pTau. Dr. Blennow’s team is also developing antibodies that can detect portions of pTau, as past work has suggested that pTau can break apart in the body. Further, the researchers will study the combination of antibodies that may best detect pTau in the biological samples. Together with the antibody experiments and another highly-sensitive technique to measure protein levels in the samples, the researchers will study the exact levels of each form of pTau in blood and CSF samples from the participants. Dr. Blennow’s team will then compare the levels of different forms of pTau to the levels of beta-amyloid (the protein that accumulates to form plaques, one of the hallmark brain changes observed in Alzheimer’s) or levels of tau observed in brain scans in the participants.
By leveraging another ongoing study at the University of Pennsylvania, the researchers will also analyze brain tissue from individuals with tauopathies to understand whether different forms of pTau may be associated with specific abnormal tau-related brain diseases. The researchers believe that these studies may help clarify whether they may be able to select the most easily measurable form of pTau in the biological samples to accurately identify tauopathies.
This study could advance the development of a cost-effective strategy to identify tauopathies including Alzheimer’s. If successful, Dr. Blennow’s approach may help clarify which forms of pTau are most useful from a diagnostic standpoint, and how different forms of tau protein may contribute to the progression of Alzheimer’s.
Made possible through the generous funding from the Zenith Society, benefiting the Alzheimer’s Association.
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