Breakthrough in diagnosing fatal brain disorder PSP

Resume: Researchers have identified protein biomarkers in spinal fluid that can diagnose progressive supranuclear palsy (PSP) in living patients. Using high-throughput technology, they found a distinct protein pattern in PSP patients, offering hope for early diagnosis and targeted treatments.

This development could lead to a diagnostic test, crucial because PSP is often mistaken for Parkinson’s and progresses rapidly. Accurate early diagnosis is essential for effective treatment and improving patient outcomes.

Key Facts:

  1. Identified protein biomarkers: Researchers discovered specific protein patterns in the spinal fluid of PSP patients.
  2. Early diagnosis: This breakthrough offers hope for early diagnosis of PSP, which is essential for effective treatment.
  3. Rapid progression: PSP progresses more rapidly than Parkinson’s disease; most patients die within seven years of the onset of symptoms.

Source: UCSF

Progressive supranuclear palsy (PSP), a mysterious and fatal neurological disorder, usually goes undiagnosed until a patient dies and an autopsy is performed. But now, researchers at UC San Francisco have found a way to identify the condition while patients are still alive.

A study that in Neurology found a pattern in the spinal fluid of PSP patients on July 3, using a new high-throughput technology that can measure thousands of proteins in a small drop of fluid.

Researchers hope the protein biomarkers will lead to the development of a diagnostic test and targeted therapies to stop the disease’s fatal outcome.

These are brain scans.
The protein signature of the autopsy-confirmed PSP cases also differed from the autopsy-confirmed cases of other forms of FTD, as well as from the living patients. Credit: Neuroscience News

The disorder came onto the public’s radar 25 years ago, when Dudley Moore, star of “10” and “Arthur,” shared his PSP diagnosis. It’s often confused with Parkinson’s disease, but PSP progresses more quickly and patients don’t respond to Parkinson’s treatments. Most PSP patients die within about seven years of their symptoms starting.

Diagnosis is key, as treatments work best early

PSP is thought to be caused by a buildup of tau proteins that causes cells to weaken and die. It is a type of frontotemporal dementia (FTD) that affects cognition, movement and behavior. The hallmark symptoms are poor balance with frequent backward falls and difficulty moving the eyes up and down.

“Unlike Alzheimer’s disease, there are no tau scans, blood tests or MRIs that provide a definitive diagnosis of PSP. For many patients, the disease goes undetected,” said co-senior author Julio Rojas, MD, PhD, of the UCSF Department of Neurology, Memory and Aging Center and the Weill Institute for Neurosciences.

“When new drugs are approved for PSP, patients are most likely to be treated at the earliest stage of the disease, when treatment is most likely to be effective,” he said.

According to co-author Adam Boxer, MD, PhD, distinguished professor of memory and aging in the UCSF department of neurology and director of the Alzheimer’s Disease and Frontotemporal Dementia Clinical Trials Program, the inability to identify PSP has hampered the development of new treatments.

“Previous research has highlighted the value of several non-specific neurodegeneration biomarkers in PSP, but these had limited sensitivity and specificity for diagnosis, especially at this critical early stage of the disease,” he said.

The researchers measured the protein biomarkers using high-throughput protein analysis technology, which is based on molecules that bind to proteins with high selectivity and specificity.

The study had 136 participants, with a mean age of 70, and included patients from UCSF and other institutions with symptoms consistent with PSP, as well as autopsy-confirmed PSP cases. Scientists compared biomarkers from these cases to the living patients, as well as to healthy participants and to patients with other forms of FTD.

The researchers found lower levels of most proteins in those with confirmed or suspected PSP, compared to the healthy study participants. The protein signature of the autopsy-confirmed PSP cases also differed from the autopsy-confirmed cases of other forms of FTD, as well as from the living patients.

All individuals with confirmed or suspected PSP had elevated levels of proteins associated with neurodegeneration. The researchers also found several inflammatory proteins that correlated with disease severity and decreased proteins relevant to several key brain cell functions that could be manipulated with future therapies.

“This work is aimed at creating a framework for using these newly identified proteins in future clinical trials,” said first author Amy Wise, formerly of the UCSF Department of Neurology and the Memory and Aging Center, and currently a medical student at UC Davis. “We hope to reach a point where a single biomarker, or a panel of biomarkers from a blood test or lumbar puncture, can provide definitive diagnostic and prognostic results for PSP.”

Financing: Dutch NIH/NIA R01AG038791, U19AG063911, R01AG073482, R56AG075744, R01AG038791, RF1AG077557, R01AG071756, U01AG045390, P01AG019724, P30AG062422.

Rainwater Charitable Foundation, GHR Foundation, Bluefield Project to Cure FTD, Gates Ventures, Association for Frontotemporal Degeneration, Alzheimer’s Drug Discovery Foundation, Alzheimer’s Association, AlzOut – Alzheimer’s Research, John Douglas French Alzheimer’s Foundation.

About this PSP and neurological research news

Author: Suzanne Leigh
Source: UCSF
Contact: Suzanne Leigh – UCSF
Image: The image is attributed to Neuroscience News

Original research: Closed access.
“CSF proteomics in patients with progressive supranuclear palsy” by Julio Rojas et al. Neurology


CSF proteomics in patients with progressive supranuclear palsy

Background and objectives

Identification of fluid biomarkers for progressive supranuclear palsy (PSP) is crucial to improve therapeutic development. We implemented unbiased DNA aptamer (SOMAmer) proteomics to identify novel CSF PSP biomarkers.


This is a cross-sectional study in original (18 clinically diagnosed) PSP-Richardson syndrome patients [PSP-RS]28 cognitively healthy controls]validation (23 PSP-RS, 26 healthy controls), and neuropathologically confirmed (21 PSP, 52 non-PSP frontotemporal lobar degeneration) cohorts.

Participants were recruited through the University of California, San Francisco and the 4-Repeat Neuroimaging Initiative. The original and neuropathology cohorts were analyzed using the SomaScan platform version 3.0 (5026-plex) and the validation cohort using version 4.1 (7595-plex).

Clinical severity was measured using the PSP Rating Scale (PSPRS). CSF proteomic data were analyzed to identify differentially expressed targets, involved biological pathways using enrichment and weighted consensus gene co-expression analyses, diagnostic value of top targets using receiver-operating characteristic curves, and associations with disease severity using linear regressions.


A total of 136 participants took part (median age 70.6 ± 8 years, 68 [50%] One hundred and fifty-five of 5,026 (3.1%), 959 of 7,595 (12.6%), and 321 of 5,026 (6.3%) SOMAmers were differentially expressed in PSP compared to controls in original, validation, and neuropathology-confirmed cohorts, with most SOMAmers showing reduced signal (83.1%, 95.1%, and 73.2%, respectively).

Three co-expression modules were associated with PSP in different cohorts: (1) synaptic function/JAK-STAT (β = −0.044, corrected P = 0.002), (2) vesicle cytoskeleton transport (β = 0.039, P = 0.007), and (3) cytokine-cytokine receptor interaction (β = −0.032, P = 0.035) pathways. Axon guidance was the most dysregulated pathway in PSP in original (strength = 1.71, P pp

A panel of axon guidance pathway proteins distinguished between PSP and controls in original (area under the curve) [AUC] = 0.924), validation (AUC = 0.815), and neuropathology-confirmed (AUC = 0.932) cohorts. Two inflammatory proteins, galectin-10 and cytotoxic T-lymphocyte-associated protein-4, correlated with PSPRS scores across cohorts.


Axon guidance pathway proteins and several other molecular pathways are downregulated in PSP compared to controls. Proteins in these pathways may be useful targets for biomarker or therapeutic development.

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