Tag Archives: tau PET

PSP’s top 10 of 2025: part 2 of 2

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Happy New Year, all!

Yesterday’s post was the first five of my top ten PSP news items of 2025. Here are the rest, again in approximate and subjective descending order of importance.

  1. New ways of interpreting standard MRI images have gained ground as diagnostic markers for PSP. One is a test of iron content in brain cells called “quantitative susceptibility mapping” (QSM). Nine papers on that topic appeared in 2025, four in 2024 and none previously. It’s looking like combining QSM data from ordinary measurements of atrophy of PSP-related brain regions could be the ticket, as both measures come from the same test procedure, unpleasant though it may be, and they measure different things.
  2. Positron emission tomography (PET) imaging of PSP’s type of tau (“4-repeat tau”) has made advances in 2025. This test requires intravenous injection of a “tracer” with a radioactive component that enters the brain tissue,sticks to the target molecule and is then imaged. It can distinguish PSP from non-PSP, distinguish among various PSP subtypes, and quantify the disease progression. The leading such tracer in terms of readiness for submission to the FDA is [18F]PI2620 and a distant second is [18F]APN-1607 ([18F]-PM-PBB3; Florzolotau). A tau PET tracer called Flortaucipir is on the market as a test for Alzheimer’s disease, but it performs poorly for PSP.
  3. There’s brain inflammation in PSP, but it’s not clear whether it’s a cause or a result of the loss of brain cells, or both. Regardless, measuring the quantity and type of inflammation using blood or PET could shed light on the cause of the disease, identify new drug targets, and serve as a diagnostic marker. A good example of 2025 research on blood markers of inflammation in PSP is here and on PET imaging of inflammation is here .
  4. We know of variants in 21 different genes, and counting, each of which subtly influences the risk of developing PSP or its age of onset. The area of the genome most important to PSP is the one that includes the gene encoding tau (called “MAPT”) on chromosome 17. The most important PSP genetic advance in 2025 was probably the discovery that some PSP risk is conferred by extra copies of a stretch of DNA, not the sequence itself. This news could inspire investigation of other places in the genome for other copy-number variants, which are much trickier to find than sequence variants. Here’s a great review of the latest in PSP genetics.
  5. And lastly, a disappointment: a negative result of a double-blind trial of the combination of two drugs already approved for other conditions: sodium phenylbutyrate (“Buphenyl”) and taurursodeoxycholic acid (“TUDCA”). Blog post here. Sponsor’s press release here. Buphenyl protects the endoplasmic reticulum, which helps manufacture proteins, and TUDCA helps prevent brain cells from undergoing self-destruction (“apoptosis”) in response to various kinds of stressors. The pair were theorized to act synergistically. The trial’s upside is that its placebo group data can be used to provide better statistical support for future innovations in clinical trial design.

A letter to Santa asking for a nice gift

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As I occasionally do, today I’ll create a blog post by combining a reader’s comment on a previous post with my reply.  This comment is from Jack Phillips, Chair of the Board of Directors of CurePSP: 

Larry, with the more rapidly progressing PSP-PF and its large % of PSP patients, it seems to put even more urgency on our Biomarker Acceleration Program. Do you believe the biomarker program will be able to distinguish between the different subtypes of PSP?
Jack

Hi, Jack,

Happy Holidays!

First, let’s assume that further research corroborates the existence, size, and statistical validity of the new subtype called PSP-PF, which isn’t a slam dunk.

You’re right that it would be great to have an accurate way to divide everyone with PSP into a) the two fastest-progressing types (PSP-RS and PSP-PF) and b) all the others.  But first, let’s see if that can be done clinically (i.e., using good old history and neuro exam).  Now that many of the people with the more aggressive variations of PSP-F and PSP-PI can be grouped as PSP-PF, the remaining, slower-progressing cases of PSP-F and PSP-PI would probably be easier to distinguish from PSP-RS than they were before, so maybe clinical would work well.

As for the ability of CurePSP’s pending biomarker program to do this job better than simple clinical evaluation: The first thing that comes to mind is to image the anatomical location(s) of the most intense tau deposition and/or inflammation in the brain.  Second-generation tau PET using the tracers 18F-PI-2620 or 18F-APN-1607 can already do those things to an extent.  That technique would now have to be refined and tested for its ability to identify PSP-PF. 

So, yes, a PET marker to diagnose PSP-PF (or maybe a PSP-PF/PSP-RS group) is a realistic goal in the next couple of years.  But the multi-million-dollar expense of all those experimental PET scans together with the administrative costs would be better handled by the companies making the PET ligands than by a relatively small nonprofit like CurePSP.   

As a more affordable alternative to PET, markers of neurodegeneration intensity might be able to distinguish PSP-RS/PSP-PF from the more slowly-progressing PSP types.  Measures of atrophy on ordinary MRI (conditioned on symptom duration at the time of the test) might be able to do this to an extent, as might serum levels of neurofilament light chain or inflammation-related compounds. 

Perhaps an index combining those two with clinical history and exam could be the ticket.  (Or perhaps all those tests would only succeed in identifying the same group of patients, in which case combining them would be pointless.  But that would be good to know.) Now, that’s something that the CurePSP Biomarker Initiative could afford to fund.