Here’s the first of two installments summarizing the original, PSP-related research presentations at the annual conference of the International Parkinson and Movement Disorder Society held in early October 2025 in Honolulu.
The listing is in no particular order and each is followed by my own editorial opinion. I’ve culled the 29 PSP-related presentations down to the twelve I considered most interesting considering both their scientific importance and their potential interest to this blog’s readers.
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Clinical Deficits, Quality of Life and Caregiver Burden across PSP Phenotypes
A. Cámara, I. Zaro, C. Painous, Y. Compta (Barcelona, Spain)
Caregiver burden is greater for PSP-Richardson syndrome than for other PSP subtypes, and quality of life showed a statistically non-significant trend for PSP-RS as well. This information may be useful in counseling patients and caregivers.
LG comment: This result would be expected given the rapid progression of PSP-RS and its high prevalence of falls and dementia relative to most other PSP subtypes. The study importantly points out that caregiver burden receives too little attention from clinicians, researchers, policy planners and insurors.
Clinical Features Suggestive of Alpha-Synucleinopathy in Progressive Supranuclear Palsy
C. Painous, A. Martínez-Reyes, J. Santamaria, M. Fernández, A. Cámara, Y. Compta (Barcelona, Spain)
Rapid eye movement behavioral disorder and reduced ability to smell are known to be very common in Parkinson’s disease and other alpha-synuclein-aggregating disorders but also occur to some extent in those with PSP. All of this study’s patients with PD and 10% if those with clinically typical PSP had a positive spinal fluid alpha-synuclein seeding amplification assay (SAA).
LG comment: The new SAA test is not perfectly specific for synucleinopathies and could produce a false positives in people with PSP. The same is true for RBD and reduced smell sensitivity.
Identification of Genetic Variants in Progressive Supranuclear Palsy in China
Y. Kang, W. Luo (Hangzhou, China)
Pathogenic or likely pathogenic variants consistent with their respective inheritance patterns were detected in 20% (8/40) of patients: three carried PSP-related variants (CCNF, DCTN1, POLG), while five harbored variants in neurodegeneration genes linked to PSP-like phenotypes (AARS1, TDP1, FA2H, TBP, ATXN8). The controls were only historical controls from the literature.
LG comment: This list of genetic variants, each conferring a very slight increased PSP risk, differs from the lists reported in Western populations, which also have important differences from one another. The differences could be related to geographically or culturally related environmental contributions (which need different genetic backgrounds to cause damage) or to differences in laboratory methods or choice of non-PSP control populations.
Unraveling the Genetic Architecture of Progressive Supranuclear Palsy in East Asians
P. Chen, R. Lin, N. Lee, J. Hsu, C. Tai, R. Wu, H. Chiang, Y. Wu, C. Lu, H. Chang, T. Lee, Y. Chang, C. Lin (Taipei, Taiwan)
Using a Taiwanese population, this study identified three likely pathogenic variants, in the genes called APP and ABCA7, and the mitochondrial genome. It also found 39 variants of unknown significance in 37 PSP patients (20.9%), involving other genes, many of which were already known to confer slight risk for PSP.
LG comment: The difference in apparent genetic risk factors between Shanghai (previous abstract by Kang et al) and Taiwan underscores the possibility of differences in methodology, although ethnic differences between those two geographical areas could be contributing. Genetic study of PSP in East Asians could benefit all ethnicities by identifying previously unsuspected cellular pathways involved in the disease.
Multimodal imaging Integrating 18F-APN-1607 and 18F-FP-DTBZ PET in Progressive Supranuclear Palsy
C. Dong, J. Ma, S. Liu (Beijing, China)
Several kinds of positron emission tomography (PET) imaging are being tested for their ability to accurately diagnose PSP. Two of them were applied concurrently to a group of 20 participants with PSP and a control group. One, called 18F-APN-1607, shows abnormal accumulation of the tau protein and the other, called 18F-FP-DTBZ, images the neurons that use dopamine. The result was that 16 of the 20 were correctly identified by the 18F-APN-1607 and three of the other four were identified by the 18F-FP-DTBZ as being probable Parkinson’s disease. The conclusion is that performing both types of PET could provide more accuracy than the tau PET alone in distinguishing PSP from PD.
LG comment: This result is consistent with the age-old medical principle that there’s no such thing as a perfectly accurate diagnostic test. Two or more tests measuring different aspects of the same disease can work in a complementary manner to improve diagnostic accuracy. Fortunately, PET is a nearly harmless, nearly painless test. Its main drawbacks are time, expense and insufficient availability of many kinds of PET outside of referral centers.
Levodopa response in pathology-confirmed Parkinson’s Disease, Multiple System Atrophy and Progressive Supranuclear Palsy
V. Arca, J. Jurkeviciene, S. Wrigley, P. Cullinane, J. Parmera, Z. Jaunmuktane, T. Warner, E. de Pablo-Fernandez (London, United Kingdom)
About one in three people with PSP experiences some degree of benefit on levodopa, a statistic that prompts most neurologists to give that drug a try. However, the benefit is often short-lived. To measure this in a formal way, these researchers reviewed the medical records of autopsy-confirmed patients with PSP, PD or MSA. Those responding well for over two years were 2% of those with PSP, 86% of those with PD and 8% of those with MSA.
LG comment: The short duration of useful benefit from levodopa in PSP means that each patient enjoying a benefit after the drug initiation should be re-evaluated at each subsequent visit for a continued benefit. As levodopa can have long-term side effects such as low blood pressure, hallucinations and involuntary movements, a dosage taper carefully monitored by the physician should be considered after the first year or so of treatment.
PSP Blog 
Hi Dr. Golbe,
The last time I commented on your blog post, it was to thank you for being an information advocate and to share a poem with you that was inspired by one of your posts.
I’m still writing my poems, but I’m now commenting with a question that I am struggling to find a clear answer to in literature (I don’t have all the same journal subscriptions as I did when I was a graduate student).
About a month ago, my mom (diagnosed with PSP-Richardsons) was prescribed Levdopa Carbidopa for her falls. Unsurprisingly, we haven’t seen much of a change in her balance since she started the medication.
However, a significant change I have noticed in the past month has been to her mood and overall cognitive functioning – more specifically, it feels as though she has become drastically more angry and resistant to any type of support from my dad and I. She sees us (and especially him) as the “enemy” or “ableist” whenever we attempt to help her with any sort of task – especially those that are dangerous for her to complete. She also misremembers and misplaces things more frequently, which then also leads to anger and accusations towards us. She had experienced rapid mood swings before, but it feels different now, almost hateful. The other day I misunderstood something simple she was asking me to do (I think it was to lock a door, but she was on the phone so she just motioned for me to close the slider in front of it). I’ll never forget the look of pure rage and hate in her eyes and how she grabbed my arm so tightly she left bruises after I pulled our slider door shut. I cried to my dad about it afterwards and he told me he had had some similar experiences with her lately too.
My background is in health behavior change, motivational interviewing, and problem-focused/emotion-focused coping skills training, and I have always used many of these skills to communicate with her as we navigate this journey, but unlike before where our conversations led to stronger communication, connection, and support, now our home just feels drained, disheartened, and a bit broken.
At first, I was resigned to the idea that her symptoms are simply progressing, and like many others with PSP, she starting to experience some FTD symptoms as part of her disease (that, and she is likely struggling greatly with fear of the future while grappling with her quick loss of many abilities and independence).
But yesterday, when I started thinking more about it, I had the thought that the timeframe of these (what feels like) sudden changes seemed to align pretty closely to when she began taking Levdoba Carbidopa.
So all this to say, I am curious if in the presentations you’ve attended, or during your own research experience, have you seen these personality-type changes appear as a side effect for this medication? I have seen some research that hallucinations and delusions have been adverse effects, but I’m hesitant to attribute her changes to medication side effects, when it could just as likely be the vicious disease itself.
Thanks again for all you do,
Delaney
Delaney:
Sorry to hear of your mom’s difficulties. There’s no need to be “hesitant to attribute her changes to medication side effects.” Like any good hypothesis, that one’s testable. All you need to do is to call the neurologist and discuss a careful, slow, monitored taper of the levodopa/carbidopa. The agitated, paranoid, delusional abnormalities you’re describing are common side effects of high-dosage levodopa, especially in people with existing, diffuse brain degenerative disorders like PSP. Levo/carb is unlikely to still be providing benefit anyway, unfortunately. But it’s important to undertake the taper only under the close professional supervision.
Dr. G
Thank you Dr. G, I appreciate your insight and will reach out to the neurologist.