September 2026 Research Update

Taken together, these studies suggest that several different types of information may each help distinguish progressive supranuclear palsy (PSP) from Parkinsons disease (PD): movement exam patterns, targeted brain measurements on MRI, newer MRI analysis methods, and selected spinal-fluid tests. Whether combining them improves accuracy was not shown; the one study that tested an MRI measure plus a blood ratio found no clear gain. A common theme was that PSP tends to show more balance and trunk movement problems with less typical rest tremor, along with brain region changes that can be measured. Most evidence here is exploratory (often retrospective, with small PSP groups), so these tools are better viewed as supportive rather than definitive on their own. [1] [2] [3] [4] [5] [6] [7] [8] [9]

A movement-exam based ratio (more trunk and balance impairment compared with rest tremor) separated PSP from PD well in a large clinic dataset using the standard motor rating scale scored in the OFF-medication state. In that study, the axial to rest-tremor ratio reached an area under the curve (AUC) of 0.909, reflecting strong separation between the two groups within that center. [1]

Several MRI approaches aimed to capture disease-specific brain changes rather than relying only on visual reads. Automated pallidal volumetry (measuring the size of a deep brain structure) was lower in PSP than PD in a very small case-control sample, and it discriminated better than a simple blood inflammation ratio in that cohort. A separate diffusion MRI study suggested that just two carefully chosen diffusion measures from specific regions could differentiate PD, PSP, and multiple system atrophy (MSA) with moderate to high accuracy depending on the pairwise comparison, although the PSP group was small. [2] [3]

Other imaging work focused on advanced MRI signals and broader brain-network patterns. Diffusion-derived free-fluid measures and putamen volume differed across PD, PSP, MSA, and controls and were more consistently separating groups than quantitative T1 measures in that dataset. Resting-state functional MRI (fMRI) analyzed with a dynamic brain-state model separated PD from PSP with an AUC around 0.91 in cross-validation, and the fMRI features were also linked to non-motor symptoms and disease severity measures in PSP. [6] [4]

Two studies examined non-motor and cognitive-linked signals that might support differential diagnosis. A scoring method applied to the simple pentagon-copy drawing on the Mini-Mental State Examination tended to be lower in atypical parkinsonian syndromes (including PSP) than PD, with high specificity but low sensitivity at one cutoff, and it correlated with a brainstem MRI index. In spinal fluid, which was available for only some participants, an alpha-synuclein seeding test was positive in all 11 Parkinsons disease participants tested and negative in the 17 PSP-Richardson syndrome participants and 5 controls tested, while about a quarter of the PSP-parkinsonism participants tested were positive; importantly, synuclein-like symptoms did not reliably match test positivity within PSP-parkinsonism. [5] [8]

Not every study centered on PSP versus PD alone, but they help map where different tests may be most informative. A retina scan study found clearer retinal thickness differences for MSA compared with controls and PSP, and retinal measures tracked swallowing problems and axial motor impairment, suggesting retina measures may reflect certain symptom burdens more than they pinpoint PSP. In a larger group spanning several frontotemporal dementia-related syndromes (including PSP), MRI- and FDG-PET pattern components helped classify syndromes, while tau-PET patterns were less syndrome-specific even when overall model performance looked high in training. [7] [9]

For patients and caregivers, this months research mainly adds background on how PSP diagnosis may become more supported by measurable markers over time, rather than changing diagnosis today. The most immediately usable ideas are those that build on tests already used in many clinics (standard movement ratings and routine MRI), but these studies still need confirmation in larger, prospective groups and ideally with pathology confirmation. What remains uncertain is which single marker or combination works best across different PSP subtypes and across different hospitals, since several results came from small PSP samples and retrospective datasets. [1] [2] [3] [4] [5] [6] [7] [8] [9]

Taken together, the papers suggest that signs of inflammation measured in blood can be different in people with progressive supranuclear palsy (PSP), and may relate to brain changes seen on scans. However, results are mainly at the group level, and it remains uncertain whether any single blood test can reliably distinguish PSP from similar conditions for one person. [10] [11]

A systematic review and meta-analysis found that glial fibrillary acidic protein (GFAP), a blood marker often linked to brain support cells, was moderately higher in PSP than in healthy controls across seven blood studies. The review also noted that separating PSP from Parkinson's disease or multiple system atrophy using blood GFAP was limited and inconsistent, and there are no established accuracy numbers for diagnosis in an individual. [10]

In a small retrospective case-control study (12 PSP and 12 Parkinson's disease), PSP showed more shrinkage in certain frontal and deep brain regions on MRI, but the common blood inflammation indices did not differ clearly between the two diseases overall. Within the PSP group, a higher monocyte-to-lymphocyte ratio (a simple ratio from a standard blood count) was linked to a lower combined score reflecting frontal brain network volume after accounting for age, meaning higher inflammation in blood tracked with more frontal network shrinkage in this small sample. [11]

For patients and caregivers, these results mainly help explain what researchers are trying to measure in PSP rather than changing care now. Blood markers like GFAP or inflammation ratios may eventually contribute to research tools that track disease or help sort PSP from similar disorders, but today they do not have proven accuracy for making or confirming a diagnosis in one person, and it is still unclear how stable they are over time or how closely they reflect symptoms. More studies that follow people over time and compare multiple conditions are needed to learn whether these blood measures are useful beyond research settings. [10] [11]

Across this group of papers, brain scanning results suggest that progressive supranuclear palsy (PSP) does not worsen evenly across the brain over short time periods. Over one year, tau build-up (a protein linked to PSP) appeared to increase most in certain deep brain areas and some outer brain regions, and change in one deep brain area tracked most closely with clinical worsening. [12]

In a prospective study following 26 people with PSP and 10 healthy controls for one year, tau signal at the start was strongest in the globus pallidus and midbrain on a tau positron emission tomography (PET) scan using florzolotau. Over the year, tau increased in the globus pallidus, frontoparietal cortex, and cerebellar white matter, while the midbrain showed little additional change during that same time window. [12]

The study also linked brain changes to symptom changes: increasing tau in the globus pallidus showed the strongest relationship to worsening on a PSP symptom rating scale. This link was most evident in people with the typical form called Richardson syndrome, suggesting that for some patients, measuring change in specific brain regions may reflect near-term clinical progression better than others. [12]

For patients and caregivers, this research mainly adds background information about how PSP may change inside the brain over time, and it helps explain why symptoms can progress while some brain areas change more than others over a similar period. Because this was a small, one-year imaging study, it cannot yet tell what an individual person's scan would mean for their future, and it does not prove how well this type of scan can track PSP in everyday clinical care.

Across studies, symptoms that may be overlooked in clinic visits were shown to be common in progressive supranuclear palsy (PSP) and closely tied to day-to-day functioning. Dystonia (sustained muscle pulling or twisting) and groaning were both frequent, and groaning was linked to greater disability and caregiver burden, while cognitive and communication changes helped explain why everyday tasks and conversations can become harder. [13] [14] [15] [16]

In a prospective clinic cohort of 88 people with PSP, dystonia was reported in 64.8% and showed different body patterns depending on PSP subtype (for example, more limb dystonia in corticobasal syndrome-type PSP and more head/neck involvement in Richardson-type PSP). People with dystonia also had brain scan measures consistent with more brainstem involvement. In the subgroup that received botulinum toxin injections for dystonia (19 people), 12 had marked improvement and 7 had partial improvement, with no worsening reported. [13]

In an Asian cohort of 180 people with PSP, groaning was reported in 20.0% and was more common in Richardson's syndrome. Groaning was linked to worse overall disease severity, lower ability to manage daily activities, and higher caregiver burden, and triggers were identified in 76.0% of those who groaned. Genetic testing in some participants found disease-related variants in a few genes, but these results do not explain most groaning and were not presented as a routine test for everyone. [14]

A neuropsychology study comparing PSP (35 people), Parkinson's disease (39 people), and healthy controls (18 people) suggested that some thinking problems often labeled as "executive" in PSP may be partly explained by a broader reduction in fluid intelligence (problem-solving across tasks). However, a measure of cognitive flexibility still showed PSP-specific difficulties even after accounting for this general factor, meaning some higher-level thinking challenges may be particularly affected in PSP. [15]

In an online survey across frontotemporal lobar degeneration spectrum conditions that included PSP, more than 65% reported communication changes, with word-finding and speaking difficulties being common. More than half said improved communication was a top priority, but reported use of speech-language therapy varied widely by clinical group. The authors emphasized that communication support may need to be tailored to a person's symptom profile. [16]

For patients and caregivers, these studies add detail about which symptoms can most affect daily life in PSP, including muscle pulling/twisting (often painful or limiting), involuntary groaning that may increase caregiver strain, and specific patterns of thinking and communication difficulty. Most evidence here comes from observational research, so it describes how common these issues were and how they related to disability in the studied groups, rather than proving cause-and-effect or predicting what will happen for any one person. It also remains uncertain how results may differ across countries, care settings, or PSP subtypes not well represented in each study. [13] [14] [15] [16]

Across frontotemporal lobar degeneration (FTLD) spectrum conditions, the APOE gene showed different patterns depending on the specific diagnosis, and progressive supranuclear palsy (PSP) stood out as having no strong, consistent link. Overall, APOE4 was more common in some FTLD conditions than in healthy controls, but PSP did not show a robust association when diagnosis was based on clinical evaluation alone. Some uncertainty remains because fewer studies had brain tissue confirmation of PSP and because results varied across FTLD subtypes. [17]

In this systematic review and meta-analysis of 40 studies, APOE4 carriage was higher in frontotemporal dementia (FTD) overall than in healthy controls, but lower than in Alzheimer's disease. For PSP specifically, APOE4 was not robustly different from healthy controls in clinically diagnosed cases; in a smaller, exploratory analysis restricted to pathologically confirmed PSP, APOE4 appeared slightly less common than in healthy controls, but this signal did not remain statistically clear after adjusting for multiple comparisons. APOE2 did not show a meaningful association with PSP in the available data. [17]

The authors noted several reasons the PSP genetics signal may be hard to pin down, including limited pathologically confirmed PSP datasets, possible misclassification when relying on clinical diagnosis alone, and overrepresentation of Western populations. They also emphasized that APOE may interact with tau-related brain changes differently across FTLD diagnoses, so results in Alzheimer's disease cannot be assumed to apply to PSP. [17]

For patients and caregivers, this research mainly helps clarify background risk clues rather than offering a test that can reliably confirm PSP or predict its course. The current evidence suggests that carrying APOE4 is not a strong or consistent risk marker for clinically diagnosed PSP, and even the weaker signal seen in pathologically confirmed PSP needs more data to confirm. More research in diverse populations and with confirmed diagnoses is needed before APOE results can be interpreted as meaningful for most people affected by PSP. [17]

Across these papers, the overall pattern is that changing specific brain signaling pathways lowered abnormal tau-related changes and reduced inflammation in lab and mouse models that develop tau buildup. Both approaches are still preclinical, so it is not yet known whether they would be safe or helpful for people with progressive supranuclear palsy (PSP). [18] [19]

One research team studied catestatin, a naturally occurring peptide, and found signals suggesting it may counter tau buildup in several experimental systems. In cortical neuron cultures and brain slice cultures, adding catestatin reduced tau phosphorylation and aggregation, and in a tauopathy mouse model it reduced pathological tau species, lowered gliosis, and improved cognitive testing. [18]

In the same work, catestatin also reduced measures of neuroinflammation and amyloid burden in a separate mouse model that develops amyloid, linking the peptide to broader changes in brain inflammation. The authors connected these effects to lower adrenergic (stress-related) signaling, including reduced epinephrine levels and reduced Protein Kinase A activity in models studied. [18]

A second group focused on DYRK1A, an enzyme that can influence tau phosphorylation, and reported higher DYRK1A protein in postmortem brain tissue from primary tauopathies including PSP compared with healthy controls. They also found DYRK1A levels tracked with measures of disease severity in the brain tissue dataset. [19]

They then tested a brain-penetrant DYRK1A inhibitor, DYR533, in a tauopathy mouse model and found reduced DYRK1A activity and protein levels along with lower levels of several disease-related tau phosphorylation markers. The study also reported broadly lower inflammatory signaling in the brain and modest improvements on motor and learning tasks, while body weight did not differ between treated and untreated groups. [19]

For patients and caregivers, these results mainly matter as background research on how future PSP treatments might be designed to target tau changes and brain inflammation. Because both studies were done in lab systems, mouse models, and/or postmortem brain tissue, it remains uncertain whether these approaches would translate into meaningful symptom or daily-function benefits in people, and human safety and effectiveness have not yet been established.

Across these studies, PSP was linked to changes outside the classic movement-related brain regions, including the gut, brain blood vessel cells, and a hypothalamic area related to sleep-wake regulation. The overall direction of results points to measurable body-system differences in PSP, but it is still uncertain how directly these differences connect to day-to-day symptoms or disease stages. [20] [21] [22]

In a very small breath-test study (5 people with PSP, 33 controls), intestinal methanogen overgrowth (an overgrowth of methane-producing organisms) was detected more often in PSP than in controls. Hydrogen-type small intestinal bacterial overgrowth was not seen in either group, and methane overgrowth did not clearly line up with constipation or overall digestive symptom severity in this pilot sample. [20]

A large postmortem brain study that included PSP examined gene activity in different types of blood vessel-related cells and found a shared vascular stress response (including increased heat-shock related genes) across PSP and other brain diseases studied. In PSP tissue, this work supports the idea that vascular cells show stress signals, although the most extensive vessel remodeling described in the paper was seen in Alzheimer disease rather than PSP. [21]

Another postmortem study focused on the intermediate nucleus, a small hypothalamic region considered similar to a sleep-promoting brain node, and found marked neuron loss in advanced PSP. The PSP cases showed an 84.1% reduction in total neurons compared with baseline comparison cases, but the study could not link these tissue changes to measured sleep symptoms because sleep data were not available. [22]

For patients and caregivers, these papers add background evidence that PSP can involve more than movement and eye control, including digestive biology, blood vessel-related brain cells, and a sleep-related hypothalamic area. Right now, the gut result comes from a very small pilot sample and did not clearly explain constipation severity, and the brain studies were done after death so they cannot show how these changes evolve over time in a living person. What remains uncertain is whether these body-system changes are drivers of symptoms, side effects of living with PSP, or parallel changes that vary by individual. [20] [21] [22]