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Nice Catch? Antibodies Stabilize Tau In The Blood; Mark Levels In Brain


Tau pathology is linked with neurodegeneration in multiple tauopathies, and efforts are underway to vanquish this tangle-forming protein with anti-tau antibodies. Besides perhaps having a therapeutic effect, these antibodies may open a window to soluble tau in the brain, according to a study published April 19 in Science Translational Medicine. Researchers led by David Holtzman at Washington University in St. Louis reported not only that an anti-tau antibody stabilized tau in the blood in tau-transgenic mice and in people with progressive supranuclear palsy (PSP), but also that levels of plasma tau bound by the antibody reflected the amount of soluble, extracellular tau in the brain.

“The antibody catches tau protein as it comes out of the brain and into the blood,” Holtzman told Alzforum. This suggests the antibody could serve as a blood-based marker to track tau levels in people with neurodegenerative diseases or following neuronal injury, he added.

As part of their goal of stopping the spread of tau aggregates between neurons in the brain, Holtzman and colleagues previously developed tau antibodies, including HJ8.5 used in this study. HJ8.5 is specific for tau’s N-terminus, and reduces tau pathology and cognitive deficits in P301S mice (see Sep 2013 news). Subsequent work revealed that besides striking down levels of hyperphosphorylated and insoluble tau in the brain, intraperitoneal injections of HJ8.5 elevated plasma tau (see Yanamandra et al., 2015). C2N Diagnostics and AbbVie subsequently humanized the antibody, dubbed C2N-8E12, which is being tested in clinical trials in people with AD and PSP.

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