“Next-Generation Tau PET Tracers Strut Their Stuff” – differentiating PSP from AD

This is a report by Alzforum from the Alzheimer’s/Parkinson’s 2017 conference in Vienna at the end of March.  The focus of the report is on next-generation tau PET tracers.  Tau is the protein involved in Alzheimer’s Disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick’s disease, and chronic traumatic encephalopathy.

There are five new PET tracers under development.  The report says:

“[The] new tracers…appear at first glance to be able to overcome the limitations of the earlier compounds. In general, the newcomers boast higher brain uptake and more specific binding, yielding cleaner-looking scans with sharper distinction between positive and negative findings. While the older tracers work only in AD, some of the new ones appear to light up other tauopathies, as well. Researchers at Piramal Imaging wowed the crowd with scans showing a distinct, specific pattern of binding of their tracer in progressive supranuclear palsy (PSP) compared to AD.”  (Check out the online version of the article for AD vs. PSP images.)

The first-generation tau PET tracers described in the report are:  Lilly/Avid’s AV-1451 (flortaucipir) and THK5351, discovered at Tohoku University in Sendai, Japan, and licensed by GE Healthcare for commercial distribution.  The report indicates that both tracers have lots of problems.

As a result, many researchers are “now eyeing Merck’s and Piramal’s [tracers]. … Merck reported on their tau PET tracer, MK-6240, at the Human Amyloid Imaging (HAI) meeting held January.”  Other companies working on tau ligands include Genentech, Roche, and Janssen.

“Piramal started a Phase 1 trial on four people with AD, three with PSP, and two healthy controls. … Notably, AD and PSP scans revealed distinct patterns. In PSP, only a few discrete regions, mainly the pallidum and substantia nigra, lit up. In contrast, AD patients took up tracer in broader areas known to accumulate tau tangles, such as the lateral temporal lobe, hippocampus, entorhinal cortex, and precuneus.  Curiously, one of the AD patients had a negative tau scan. Stephens noted this patient had mild AD, with an MMSE of 26, and may not have accumulated much pathological tau yet. Incidentally, other PET experts, too, noted that as more research groups image both amyloid and tau pathology in the same cognitively impaired people, they are finding a few whose scans are amyloid-positive but tau-negative.”

Here’s a link to the full report:


Next-Generation Tau PET Tracers Strut Their Stuff
Series – AD/PD 2107 Draws Record Number of Scientists To Vienna
14 Apr 2017
by Alzforum