If not amyloid, how about tau?

With the apparent failure of Aducanumab to improve cognition, interest is turning to the protein tau.  Aducanumab used antibodies to remove beta-amyloid plaques from brains with apparent success.  It just didn't make people's memories better or otherwise effectively treat their AD.  But perhaps using antibodies to remove tau proteins will get better results.

We discuss tau proteins in Beating the Dementia Monster.  The protein holds the microtubules together that, among other things, form a skeleton within cells.  When an abnormal form of the protein is present, it allows the microtubules to collapse into a "tangle."  The abnormal tau escapes from the cell, and it may be that the spread of abnormal tau propagates AD throughout the brain.

So can antibodies remove abnormal tau from the brain?  If so, can removing the abnormal tau stop the progress of AD?  Researchers are trying to find out.

This week's issue of ALZForum carries an interesting article about progress in using antibodies to remove tau fragments from the cerebrospinal fluid (CSF).  Some researchers have completed a first stage trial of an antibody called BIIB092.  As with all phase one trials the study employed a small number of test subjects (48), but all seemed to do well with the treatment.  There were some issues, but these did not appear to be related to the treatment.  The good news is that the drug removed about 90% of one tau protein fragment from the CSF.  However, the trial only lasted three months, and there was no improvement in MRIs or other biomarkers.  This was expected with such a short trial.  It's also not clear if removing this particular fragment is the key to stopping the spread of the disease throughout the brain.

So phase 2 is now underway.  It involves 528 AD patients, and it is planned to extend over an 18-month period.  The treatment should continue to remove the tau fragments, and researchers will remain vigilant for adverse affects.   But will the treatment improve cognition or otherwise beat back the advance of AD?  We are all waiting to find out.