January 2026 Research Update

Across these studies, researchers tested whether body-fluid markers, eye scans, and different brain imaging approaches can help (1) tell progressive supranuclear palsy (PSP) apart from people without PSP and (2) measure disease burden or change over time. Overall, several tools showed clear group differences, and some measures lined up with thinking tests or overall severity. However, much of the evidence is cross-sectional (one timepoint), so it remains uncertain how well these tests track change in an individual over time or work across different clinics. [1] [2] [3] [4] [5]

In a small case-control study, levels of nerve-injury and brain-support-cell proteins measured in spinal fluid and blood were higher in PSP than in controls, and certain ratios performed especially well at separating PSP from controls. A blood ratio also tracked the amount of tau signal on a tau brain scan in deep brain regions, and related to disease severity and processing speed, suggesting a combined approach (blood tests plus imaging plus clinical testing) may help with monitoring. [1]

Two brain-scan studies focused on improving what positron emission tomography (PET) can detect in PSP. One exploratory study using a tracer aimed at cholinergic nerve terminals found lower signal in PSP than in healthy controls, most consistently in the entorhinal cortex and caudate, and some brainstem-related measures lined up with cognitive scores and disease duration. [2]

A larger prospective imaging study tested a data-processing step meant to remove non-disease signal from a tau PET scan. After this subtraction step, diagnostic accuracy improved in some brain regions, and scan signal related more strongly to underlying tau pathology severity in selected areas, suggesting that analysis methods can meaningfully change what a scan shows in PSP. [3]

A separate cross-sectional study used optical coherence tomography (OCT), an eye imaging test, and found that certain retinal layers were thinner in PSP than in healthy controls, and that some retinal measures differed between PSP and Parkinson's disease. The study also reported that one retinal layer measure did not separate Parkinson's disease from atypical parkinsonism overall, highlighting that not all OCT measurements are equally helpful for distinguishing conditions. [4]

Finally, a longitudinal study used MRI-based patterns of brain changes to help sort likely PSP versus corticobasal degeneration (CBD) biology and to create MRI signatures that may measure progression more sensitively than common clinical scales in research settings. In the datasets studied, these MRI signatures correlated with change in a PSP rating scale over 12 months and were estimated to reduce sample sizes needed for clinical trials compared with traditional outcomes, though the authors noted the need for independent validation and more confirmation of underlying diagnoses. [5]

For patients and caregivers, this group of studies mainly adds background about how PSP might be measured more precisely in research and, over time, possibly in clinical care. The most immediately understandable idea is that different types of tests (blood or spinal fluid markers, MRI, PET, and OCT eye scans) can capture different parts of the disease, and some measures relate to thinking or overall severity. What is still uncertain is how well any one test performs for individual decision-making in everyday care, especially because many results came from small or single-timepoint studies and because newer scan-analysis methods may change results across sites.

Across two cross-sectional MRI studies, progressive supranuclear palsy (PSP) showed measurable changes beyond the midbrain, including the cerebellum and connecting pathways. Some brain measurements moved in step with how severe symptoms were or how well people performed on a brief thinking test, while other changes varied by PSP clinical variant. Because these studies were done at one point in time, they describe links rather than showing what changes come first. [6] [7]

In a study comparing PSP with Parkinson's disease and healthy adults, people with PSP had smaller volumes in several areas including the midbrain and specific cerebellar regions. Smaller volumes in parts of the back of the cerebellum were linked to lower scores on a short test of executive thinking, suggesting that cerebellar changes may relate to cognitive symptoms in PSP. More severe PSP symptoms were linked to smaller volumes in the midbrain and a connecting pathway called the superior cerebellar peduncle. [6]

A separate study looked at the cerebellar dentate (a deep cerebellar structure) across multiple PSP variants and found variant-specific patterns of higher magnetic susceptibility (often interpreted as reflecting more iron), volume loss, and shape deformation compared with healthy controls. Some variants showed higher susceptibility without clear volume loss, while another showed prominent shape differences even when susceptibility was not increased, suggesting that different biological changes may dominate in different PSP presentations. The authors also reported that these dentate measurements could help distinguish certain PSP variants from each other in their dataset, but emphasized the need for larger studies to confirm this. [7]

For patients and caregivers, these results add detail about which brain areas may be linked to specific symptoms in PSP, including thinking changes and overall severity. Right now, this is mainly background research: the MRI measurements were studied in groups and are not yet proven to predict an individual person's symptom course. It also remains uncertain how these measures change over time, and how well they generalize across clinics, scanners, and PSP variants.

Across these studies, measures of balance and walking helped explain who had more falls or greater mobility limits, but they did so in different ways. In progressive supranuclear palsy (PSP), a structured balance test at discharge was linked to falls soon after leaving the hospital. Separately, wearable sensors suggested that daily-life movement patterns can look different from what clinic-based walking assessments and standard rating scales capture. [8] [9]

In a prospective cohort of 54 people with PSP, lower total scores on the Mini-Balance Evaluation Systems Test (Mini-BESTest) at discharge predicted more frequent falls over the next month. A specific part of the test focused on anticipatory postural adjustments (preparing the body for movement) showed a link to falls in one statistical model, but was less clear after adjusting for other factors. Another balance test (Berg Balance Scale) also looked related to falls in one model, but not after further adjustment. [8]

In an exploratory multicenter study including 20 people with PSP (and comparison groups with multiple system atrophy and Parkinson's disease), clinic-based sensor gait testing showed that the atypical parkinsonism groups had slower walking speed, shorter steps, and more variability and asymmetry than Parkinson's disease. Home monitoring over a week showed fewer daily steps, fewer longer walking bouts, and a lower active-to-sedentary ratio in atypical parkinsonism, and these home measures did not line up closely with the clinic gait measures. The authors concluded that combining clinic sensors with at-home monitoring can add information about day-to-day mobility that standard clinical scales may not capture. [9]

For patients and caregivers, these results mainly help explain why fall risk and mobility problems can be hard to judge from a single snapshot in clinic. A structured balance test (Mini-BESTest) may be one practical way clinicians summarize near-term fall risk in PSP, while wearable sensors highlight that real-life activity level and walking patterns at home can differ from clinic performance. What remains uncertain is how well these measures predict longer-term outcomes, and whether specific sensor measures can reliably guide care in PSP, since the wearable study was exploratory and included mixed diagnoses and unequal disease severity across groups. [8] [9]

Across these papers, research ranged from day-to-day care decisions (feeding tubes for swallowing problems) to early-stage treatment development (a brain peptide studied in the lab and in mice) and a planned remote trial for sleep medicines in people with progressive supranuclear palsy (PSP). The clearest near-term evidence came from an observational study of feeding tubes, while the other two papers set up potential future options but do not yet show patient outcomes in PSP. [10] [11] [12]

In a retrospective cohort of 72 people with atypical parkinsonian syndromes (including PSP), those who received a percutaneous endoscopic gastrostomy (PEG) feeding tube had longer median survival counted from when swallowing problems began. However, PEG was not linked to fewer hospital admissions for aspiration pneumonia, meaning it may not reduce the risk of food or liquid going into the lungs even if it supports nutrition. [10]

One translational experimental study explored catestatin, a naturally occurring peptide, as a way to influence tau and amyloid changes seen in several brain diseases, including PSP, using postmortem human brain tissue plus cell, slice, and mouse models. Catestatin supplementation lowered measures of abnormal tau in multiple models and improved movement and thinking tests in a tau mouse model, with proposed links to reduced stress-hormone signaling and inflammation. This was not a clinical trial in people with PSP, so it does not show whether the same effects would occur in patients. [11]

A separate paper described a 6-week, remote, double-blind randomized cross-over trial protocol for disturbed sleep in adults with PSP, comparing suvorexant, zolpidem, and placebo across short treatment periods. The report focused on how the study will measure sleep and safety using wearable activity tracking, ambulatory sleep brain-wave monitoring, questionnaires, and caregiver-partner participation, but it did not report results yet. [12]

For people with PSP and caregivers, this group of studies separates what is known now from what is still being tested. The feeding tube study adds real-world information about survival and aspiration pneumonia hospitalizations after swallowing problems begin, but because it was retrospective (not randomized), it cannot prove PEG caused the survival difference and does not clarify which patient situations benefit most. The catestatin work is mainly background research toward future therapies, and the sleep medicine paper is a study plan that could help answer practical questions about sleep treatment in PSP once results are available; for now it mainly shows that remote, caregiver-supported trials are feasible to attempt but still unproven in outcomes. [10] [11] [12]

Across these postmortem brain studies, a consistent message is that PSP is not identical from person to person at the molecular level. Differences in tau (a brain protein that clumps in PSP) included how strongly it could act as a "seed" to help tau spread, and the specific chemical changes and cut forms present on tau. [13] [14]

One exploratory study separated PSP brains into higher- vs lower-tau-seeding groups, and the higher-seeding group had shorter disease duration. Higher-seeding cases also showed different brain protein and gene-activity patterns related to immune function and metabolism, and their brain tissue was more toxic in a lab test using astrocytes (support cells in the brain). [13]

A larger proteomics study mapped many types of tau modifications and cleavage patterns across multiple tau-related diseases and found that each disease had its own tau "signature." In that cross-disease comparison, PSP showed fewer tau modifications and cleavage events than several other tau diseases, and computer-based classifiers could distinguish diseases using these tau patterns. [14]

For patients and caregivers, these results mainly help explain why PSP symptoms and pace of change can vary between people: the underlying tau biology in the brain may not be the same in every PSP case. Right now, this is background research because it is based on postmortem tissue and lab tests, and it is not yet clear how well these tau patterns can be measured during life (for example in spinal fluid or blood) or used to predict an individual person's course. [13] [14]

Across these papers, the main message is that a PSP-like picture can sometimes be caused by, or occur alongside, other brain conditions. Two papers were single-patient case reports, so they show what is possible rather than what is common, while one study used autopsy tissue and lab work to explore an immune-related disease that can resemble PSP. [15] [16] [17]

One autopsy-based study focused on anti-IgLON5 disease, which can cause symptoms that overlap with PSP and can also show tau protein buildup in the brain. The authors reported an early pattern of tau changes inside the cell nucleus along with changes to the nuclear membrane and IgG4 antibody deposits on neurons, followed later by tau changes in the cell body, supporting the idea of an immune-triggered, time-dependent secondary tau problem. They also noted that tau patterns alone may not clearly separate anti-IgLON5 disease from PSP. [17]

In a single-patient report, a 73-year-old woman had a motor neuron disease diagnosis (amyotrophic lateral sclerosis, ALS) due to a C9orf72 gene repeat expansion, but her first symptoms looked PSP-like. The report combined exam findings, brain MRI, and nerve and muscle testing with genetic testing showing a large repeat expansion, highlighting that some genetic ALS cases may begin with symptoms that resemble PSP. [15]

Another single-patient report described Wernicke's encephalopathy (often linked to low thiamine) that uncovered a more complex situation, with evidence supporting probable PSP and probable Alzheimer's disease at the same time. The workup included brain MRI changes described as suggestive of Wernicke's encephalopathy, a dopamine transporter scan showing one-sided dopamine system dysfunction, and spinal fluid markers showing higher tau proteins and a lower amyloid ratio; thiamine treatment and supportive care were described. [16]

For patients and caregivers, this set of studies is mainly background information explaining why PSP-like symptoms sometimes require careful evaluation over time: different diseases can resemble PSP early on, and more than one condition can sometimes be present together. What remains uncertain is how often these overlaps occur and how reliably they can be separated during life, since two reports describe single individuals and the anti-IgLON5 work was largely based on post-mortem and lab evidence. [15] [16] [17]

Across this month's paper, the main message is that it is possible to reproduce some PSP-like tau changes in a mouse brain by placing PSP-related tau into brain areas affected in PSP, but the model is still constrained by how little seed material can be obtained from human PSP brain tissue. The study also suggests that different preparation methods for tau extracts can strongly change how much tau buildup is seen, and how far it appears to spread. [18]

In this exploratory animal study, researchers injected human PSP tau extracts into specific brain regions of genetically modified mice that make all six human tau forms. A 2% Sarkosyl-insoluble PSP tau preparation produced the most PSP-like pattern, with many abnormal tau deposits near injection sites and smaller amounts in connected areas such as the thalamus and hypothalamus. [18]

The study also showed that weaker preparations (such as PBS or PBS-soluble tau) led to little abnormal tau signal, while some other preparations caused only moderate changes. In the same type of experiment, Alzheimer disease tau produced stronger tau tangles than PSP tau, and the PSP-injected mice did not form classic tangle-like inclusions within the timepoints studied. [18]

A practical barrier was the very low yield of seeding-competent PSP tau from donated brain tissue, which limited the number of animals and makes it difficult to scale this approach. The authors noted that alternative ways to generate or amplify PSP tau seeds may be needed for more reproducible models. [18]

This work is background research that helps scientists build tools to test ideas about how PSP-related tau may start and move through the brain, and to evaluate potential therapies in the lab before human studies. For patients and caregivers now, it does not change diagnosis or care, but it clarifies that current PSP tau inoculation models may be hard to reproduce widely because the needed human PSP tau material is scarce, and because the resulting tau changes may stay mostly near where they are introduced. What remains uncertain is how well these mouse changes match the full range of PSP in people, including longer-term brain changes and symptoms. [18]