Scientists discover a way to spot elusive neurological disorder

Progressive supranuclear palsy (PSP) is a deadly neurological disorder often diagnosed only after death through autopsy. However, University California San Francisco researchers have found a way to identify PSP in living patients.

A study published in Neurology on July 3 discovered a protein pattern in the spinal fluid of PSP patients using advanced technology that measures thousands of proteins from a tiny fluid sample. Researchers hope these protein biomarkers will lead to a diagnostic test and targeted therapies to slow the disease.

The disorder became known to the public 25 years ago when actor Dudley Moore revealed his PSP diagnosis. Often mistaken for Parkinson’s disease, PSP progresses faster and doesn’t respond to Parkinson’s treatments. Most patients die within seven years of symptom onset.
Early diagnosis is crucial for effective treatment.

PSP is thought to be caused by a buildup of tau proteins, which leads to cell damage. It is a type of frontotemporal dementia (FTD) that affects cognition, movement, and behavior. Key symptoms include poor balance with backward falls and difficulty moving the eyes up and down.

Dr. Julio of UCSF said, “Unlike Alzheimer’s, there are no scans, blood tests, or MRIs that can definitively diagnose PSP, so many patients go unnoticed. Early treatment is crucial for PSP to be effective.”

Dr. Adam Boxer added, “The inability to diagnose PSP has hindered new treatments. While some biomarkers indicate neurodegeneration in PSP, they are not sensitive or specific enough, especially in the early stages.”

The researchers used advanced technology to measure protein biomarkers that bind specifically to proteins. The study included 136 participants, with an average age of 70, with PSP symptoms or autopsy-confirmed PSP. They compared these biomarkers to healthy people and patients with other forms of FTD.

A brain scan showing the presence of progressive supranuclear palsy in the area circled in red. Image by UCSF

They found that most protein levels were lower in PSP patients than in healthy participants. The protein patterns in confirmed PSP cases differed from those of other forms of FTD and living patients.

All participants with confirmed or suspected PSP had higher levels of proteins linked to neurodegeneration. Researchers also found inflammatory proteins related to disease severity and decreased levels of proteins essential for brain cell functions, which could be targeted with future treatments.

Amy Wise, former UCSF researcher and current UC Davis medical student, said, “This study aims to use these proteins in future clinical trials. We hope to develop a blood test or lumbar puncture that can definitively diagnose and predict PSP.”

Journal reference:

Amy Wise, Jingyao Li, et al., CSF Proteomics in Patients With Progressive Supranuclear Palsy. Neurology. DOI: 10.1212/WNL.0000000000209585.

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