This post may be of interest to those in the PSP and CBD community who are interested in what’s happening in research, particularly imaging of tau, as well as a hypothesis of how tau spreads in the spread.
Alzheimer’s is a disorder of two kinds of proteins — tau and amyloid (or beta amyloid, Aβ). PSP and CBD are disorders of one kind of protein — tau.
At the recent Alzheimer’s Association International Conference in Washington DC (mid-July), scientists reported on data from tau PET imaging. Three ligands or chemical tracers from La Roche are being studied, with one seeing superior results. The data also provide clues as to how tau may spread in the brain.
The Alzforum has a good summary of the tau imaging research presented at the conference:
“…tau imaging data bolstered the idea that tau sits tight in the medial temporal lobe until Aβ builds up, then it spreads, wreaking havoc on cognition. New imaging data suggests that once it breaks loose, tau spreads through functional networks and impairs brain metabolism. What’s more, unlike Aβ, which appears diffusely throughout the brain, tau deposits seem to map closely onto regions where atrophy occurs and cognitive deficits originate. ‘Unlike amyloid imaging, tau PET seems to strongly correlate with cognition and clinical states,’ said Gil Rabinovici, University of California, San Francisco. Researchers were also excited by a new tau ligand that appears to have better specificity and kinetics than its predecessors.”
Here’s a bit more on tau building up in certain brain regions, as in corticobasal syndrome (CBS), and the relevance of tau as a target:
“Disaster Strikes Wherever Tau Lands
Once outside the medial temporal lobe, tau seems to cause trouble wherever it lands. At AAIC, Daniel Schonhaut, who works with Rabinovici, expanded on the notion that tau builds up in brain regions thought to underlie clinical symptoms in patients with atypical forms of AD. He compared performance on a variety of cognitive tests with T807/AV1451 scans from 19 patients with typical and atypical forms of AD, including posterior cortical atrophy, primary progressive aphasia, and corticobasal syndrome. Schonhaut reported that people with typical AD who performed more poorly on memory tasks had more tau in the hippocampus and surrounding medial temporal areas, while patients with worse visual function indicative of posterior cortical atrophy had more tau in occipital regions. A third group — those with language difficulties typical of primary progressive aphasia — had more tau in the left temporoparietal region. ‘The distribution patterns of tau we’re seeing with this PET tracer seem to underlie the clinical phenotype of our patients,’ Schonhaut told Alzforum. ‘These data show nicely that there’s a relationship between where the tau is clinical symptomatology,’ said Jagust. ‘We haven’t seen that with amyloid.’ Rabinovici noted that these results corroborate findings from classic postmortem studies demonstrating that cognitive state correlates much more strongly with tangle than amyloid pathology. They also support tau as a therapeutic target, particularly in the symptomatic phase of AD, he told Alzforum.”
The entire Alzforum research summary is worth reading, if research is of interest: