Advanced MRI analysis could significantly improve early and accurate diagnosis of the rare neurodegenerative disorders progressive supranuclear palsy and corticobasal degeneration, potentially transforming clinical trials for conditions that currently have no disease modifying treatments.
An international study led by the Sant Pau Research Institute in Barcelona found that structural magnetic resonance imaging combined with advanced analytical models enables more precise identification of progressive supranuclear palsy and corticobasal degeneration. The findings were published in The Journal of Prevention of Alzheimer’s Disease in 2026.
Both conditions are atypical parkinsonian disorders and are frequently misdiagnosed as Parkinson’s disease or age related mobility problems.
“These are diseases that cause balance problems, falls, stiffness, or difficulties with speech and movement. Many patients initially present as if they had Parkinson’s disease or are simply older adults with mobility difficulties,” explains Dr Jesus Garcia Castro, researcher in the Neurobiology of Dementias Group at Sant Pau Research Institute and neurologist at Hospital de Sant Pau. Dr Castro is the first author of the study. “This means they are greatly underdiagnosed, and for years we have not known with enough certainty which disease each patient actually had.”
Progressive supranuclear palsy and corticobasal degeneration are tauopathies, marked by abnormal accumulation of tau protein in the brain. While tau is essential for normal neuronal function, its pathological buildup damages areas involved in movement control, posture, balance, speech, and certain cognitive functions. Both are classified as four repeat tauopathies and are distinct from Alzheimer’s disease despite sharing tau pathology.
“These diseases are, in a way, halfway between Alzheimer’s and Parkinson’s,” says Dr Ignacio Illan Gala, researcher in the Neurobiology of Dementias Group at Sant Pau Research Institute and neurologist at Hospital de Sant Pau, and senior author of the study. “They resemble Parkinson’s because of their motor symptoms, but they share with Alzheimer’s the fact that they are caused by tau pathology. The problem is that, until now, we did not have reliable tools to distinguish them properly.”
The absence of objective in vivo biomarkers has limited early diagnostic accuracy and complicated clinical trials. In corticobasal degeneration, a notable proportion of clinically diagnosed cases are later found to stem from Alzheimer’s pathology, leading to biologically mixed trial groups that may obscure treatment effects.
The researchers developed models that analyse patterns of brain atrophy on structural MRI scans to identify disease specific signatures.
In progressive supranuclear palsy, the most prominent damage appears in deep brain structures such as the brainstem, along with selective cortical changes. In corticobasal degeneration, atrophy more strongly affects cortical regions associated with motor control and sensory integration.
“Although they may look very similar clinically, at the brain level PSP and CBD damage the brain in different ways,” says Dr Illan Gala. “These differences are reflected on MRI, and by combining them into a signature, we can much better determine which disease each patient has.”
MRI serves two main purposes. It improves diagnostic accuracy at early stages and allows objective measurement of disease progression.
The study found that MRI signatures can function as sensitive longitudinal outcome measures. In hypothetical clinical trials targeting a 30% reduction in disease progression over 12 months, using these imaging markers could reduce required sample sizes by about 50% for progressive supranuclear palsy and between 80% and 87% for corticobasal degeneration compared with clinical scales alone.
“For a company or an academic consortium to commit to a clinical trial, it has to be feasible,” says Dr Illan Gala. “If a trial requires a thousand patients, it is practically impossible. But if it can be conducted with a reasonable number of well selected individuals and objective measures of progression, then there is a real chance of demonstrating whether a treatment works.”
The findings align with ongoing work at Sant Pau Research Institute. In the 2025 call of the PERIS programme from the Department of Health of the Government of Catalonia, the centre secured funding for a project led by Dr Illan Gala that combines plasma biomarkers and advanced imaging to improve early diagnosis of four repeat tauopathies, including progressive supranuclear palsy and corticobasal degeneration.
“Our goal is to reach a situation similar to that of Alzheimer’s disease, where a combination of a blood test and an MRI scan allows these diseases to be diagnosed at very early stages and with much greater confidence,” says Dr Garcia Castro.
“These conditions are far more common than we think, but we do not know how to detect them properly,” Dr Castro concludes. “Improving diagnosis is the first step so that these patients, who currently have no therapeutic options, can begin to have them.”
Although no disease modifying treatments exist yet, more precise MRI based diagnosis could accelerate drug development by enabling more targeted and efficient clinical trials.