Thought you might want to know that a US scientist has identified a new dementia in the US, and given it a name that includes “PSP.” The new dementia is a prion disorder, is similar to CJD, Creutzfeldt-Jakob disease — a “fast advancing dementia but with additional loss of movement and speech.” Confusingly, the name given to the disorder is “PSPr” for protease-sensitive prionopathy I read about this on a PSP-related Yahoo!Group tonight. What follows is a MedicalNews Today article as well as the abstract from the scientific journal about this new dementia.
New Fatal CJD-Like Dementia Discovered In America
10 Jul 2008
A new dementia that is distinct from but resembles known forms of CJD, Creutzfeldt-Jakob disease, has been discovered in America, affecting 16 people, 10 of whom have died after gradually losing their mental and motor functions and being unable to think, speak or move.
Yesterday’s issue of New Scientist reported that Pierluigi Gambetti, the director of the US National Prion Disease Pathology Surveillance Center based at Case Western Reserve University in Cleveland, Ohio, said nobody knows how the disease starts or spreads, or how many people may have it.
Gambetti and colleagues wrote a paper on the discovery of the disease, called PSPr (for protease-sensitive prionopathy), in a paper that was published online in the Annals of Neurology on 20th June 2008.
Gambetti said he believed the disease had been around for some time and may have been mistaken for other forms of dementia. The 16 cases include the 11 he described in the paper and another 5 that have since been diagnosed. Ten of the 16 patients have died of the disease. Their brains had the trademark damage that is normally associated with CJD (note this is not variant or vCJD that is linked to mad cow disease or BSE), except that in the case of PSPr, Gambetti and colleagues suggest the cause is genetic.
According to BBC news, experts in the UK are now checking records to see how many cases there may be in the UK, where there are between 50 and 100 cases of so-called sporadic CJD every year.
A representative of the UK’s National CJD Surveillance Unit, in Edinburgh, Dr Mark Head, said they were reviewing cases of sporadic CJD for clues that there might be some that are really PSPr. He also said it may mean there are other prion disease genes waiting to be discovered.
Sporadic CJD has no known cause, unlike the BSE-linked vCJD that is contracted from eating infected cows’ brains or spinal cord tissue.
In the US, PSPr came to light when cases were referred to CJD surveillance centers because the symptoms appeared to be CJD-like (fast advancing dementia but with additional loss of movement and speech). But tests for CJD proved negative.
Yet post mortems on the patients who died showed the familiar sponginess in the brain tissue that results when misshapen brain proteins or “prions” accumulate in the brain.
Gambetti suggested there might be a genetic link because the patients all had a family history of dementia but did not carry they CJD gene.
In the paper published earlier this year, Gambetti and colleagues reported their investigation of 11 cases at the National Prion Disease Pathology Surveillance Center for clinical, histopathological, immunohistochemical, genotypical, and prion protein (PrP) characteristics.
They wanted to report on what they believed to be a new form of prion disease where like the more common prion diseases there was a misshapen prion protein, but there was a difference in that the protein was sensitive to protease digestion.
In their conclusion they wrote that their histological, immunochemical, physicochemical and genetic investigation indicated that:
“This is a previously unidentified type of disease involving the PrP [prion protein], which we designated protease-sensitive prionopathy (or PSPr). Protease-sensitive prionopathy is not rare among prion diseases, and it may be even more prevalent than our data indicate because protease- sensitive prionopathy cases are likely also to be classified within the group of non-Alzheimer’s dementias.”
“A novel human disease with abnormal prion protein sensitive to protease.”
Pierluigi Gambetti, Zhiqian Dong, Jue Yuan, Xiangzhu Xiao, Mengjie Zheng, Amer Alshekhlee, Rudy Castellani, Mark Cohen, Marcelo A. Barria, D. Gonzalez-Romero, Ermias D. Belay, Lawrence B. Schonberger, Karen Marder, Carrie Harris, James R. Burke, Thomas Montine, Thomas Wisniewski, Dennis W. Dickson, Claudio Soto, Christine M. Hulette, James A. Mastrianni, Qingzhong Kong, Wen-Quan Zou.
Annals of Neurology, Volume 63 Issue 6, Pages 697 – 708.
Published Online: 20 Jun 2008.
Source: BBC, New Scientist, Annals of Neurology abstract.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
Here’s the abstract of the article in the Annals of Neurology:
A novel human disease with abnormal prion protein sensitive to protease
Pierluigi Gambetti, MD 1 *, Zhiqian Dong, PhD 1, Jue Yuan, BA 1, Xiangzhu Xiao, PhD 1, Mengjie Zheng, PhD 1, Amer Alshekhlee, MD 1, Rudy Castellani, MD 2, Mark Cohen, MD 1, Marcelo A. Barria, PhD 3, D. Gonzalez-Romero, PhD 3, Ermias D. Belay, MD 4, Lawrence B. Schonberger, MD, MPH 4, Karen Marder, MD 5, Carrie Harris, BA 1, James R. Burke, MD, PhD 6, Thomas Montine, MD 7, Thomas Wisniewski, MD 8, Dennis W. Dickson, MD 9, Claudio Soto, PhD 3, Christine M. Hulette, MD 10, James A. Mastrianni, MD, PhD 11, Qingzhong Kong, PhD 1, Wen-Quan Zou, MD, PhD 1 *
1Institute of Pathology, Case Western Reserve University, Cleveland, OH
2Department of Pathology, University of Maryland, Baltimore, MD
3Department of Neurology, Neuroscience and Cell Biology, George and Cynthia Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX
4Centers for Disease Control and Prevention, Atlanta, GA
5Department of Neurology, Columbia University, New York, NY
6Department of Medicine, Division of Neurology, Duke University, Durham, NC
7Harborview Medical Center, University of Washington, Seattle, WA
8Department of Neurology, New York University, New York, NY
9Department of Neuropathology, Mayo Clinic College of Medicine, Jacksonville, FL
10Department of Pathology, Duke University, Durham, NC
11Department of Neurology, University of Chicago, Chicago, IL
*Correspondence to Pierluigi Gambetti, Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106
*Correspondence to Wen-Quan Zou, Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106
NIH; Grant Number: AG14359, AG08702, NS049173
Centers for Disease Control and Prevention; Grant Number: CCU 515004
To report a novel prion disease characterized by distinct histopathological and immunostaining features, and associated with an abnormal isoform of the prion protein (PrP) that, contrary to the common prion diseases, is predominantly sensitive to protease digestion.
Eleven subjects were investigated at the National Prion Disease Pathology Surveillance Center for clinical, histopathological, immunohistochemical, genotypical, and PrP characteristics.
Patients presented with behavioral and psychiatric manifestations on average at 62 years, whereas mean disease duration was 20 months. The type of spongiform degeneration, the PrP immunostaining pattern, and the presence of microplaques distinguished these cases from those with known prion diseases. Typical protease-resistant PrP was undetectable in the cerebral neocortex with standard diagnostic procedures. After enrichment, abnormal PrP was detected at concentrations 16 times lower than common prion diseases; it included nearly 4 times less protease-resistant PrP, which formed a distinct electrophoretic profile. The subjects examined comprised about 3% of sporadic cases evaluated by the National Prion Disease Pathology Surveillance Center. Although several subjects had family histories of dementia, no mutations were found in the PrP gene open reading frame.
The distinct histopathological, PrP immunohistochemical, and physicochemical features, together with the homogeneous genotype, indicate that this is a previously unidentified type of disease involving the PrP, which we designated protease-sensitive prionopathy (or PSPr). Protease-sensitive prionopathy is not rare among prion diseases, and it may be even more prevalent than our data indicate because protease-sensitive prionopathy cases are likely also to be classified within the group of non-Alzheimer’s dementias. Ann Neurol 2008;63:697-708
Received: 5 November 2007; Revised: 1 April 2008; Accepted: 4 April 2008