Original Article
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
email: Pierluigi Gambetti ([email protected]) Wen-Quan Zou ([email protected])
*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
Funded by: NIH; Grant Number: AG14359, AG08702, NS049173 Centers for Disease Control and Prevention; Grant Number: CCU 515004 Britton Fund CJD Foundation
Abstract
Objective 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.
Methods Eleven subjects were investigated at the National Prion Disease Pathology Surveillance Center for clinical, histopathological, immunohistochemical, genotypical, and PrP characteristics.
Results 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.
Interpretation 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 Digital Object Identifier (DOI)
10.1002/ana.21420 About DOI
http://www3.interscience.wiley.com/journal/119883040/abstract
Pages: 677-678 A new prionopathy Robert Will, Mark Head http://www3.interscience.wiley.com/cgi-bin/abstract/119882940/ABSTRACT
A novel human disease with abnormal prion protein sensitive to protease (prionopathy)
http://cjdmadcowbaseoct2007.blogspot.com/2008/06/novel-human-disease-with-abnormal-prion.html
re-Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease
http://betaamyloidcjd.blogspot.com/2008/04/re-association-between-deposition-of.html
Subject: Sporadic creutzfeldt-jakob disease in two adolescents (see sCJD, the big lie) Date: May 28, 2007 at 7:58 am PST
http://brain.hastypastry.net/forums/showthread.php?t=15076
http://brain.hastypastry.net/forums/archive/index.php/t-17057.html
HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/06/human-and-animal-tse-classifications-ie.html
Tuesday, June 17, 2008
Portsmouth woman did not die of mad cow-related condition, USDA says UPDATE
Updated Jun.17, 2008 08:34 KST
http://cjdmadcowbaseoct2007.blogspot.com/2008/06/portsmouth-woman-did-not-die-of-mad-cow.html
The statistical incidence of CJD cases in the United States has been revised to reflect that there is one case per 9000 in adults age 55 and older. Eighty-five percent of the cases are sporadic, meaning there is no known cause at present.
http://www.cjdfoundation.org/fact.html
see full text ;
http://prionunitusaupdate2008.blogspot.com/2008/04/progress-report-from-national-prion.html
sporadic CJD, the big lie
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0705&L=sanet-mg&T=0&P=25276
TSS
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
email: Pierluigi Gambetti ([email protected]) Wen-Quan Zou ([email protected])
*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
Funded by: NIH; Grant Number: AG14359, AG08702, NS049173 Centers for Disease Control and Prevention; Grant Number: CCU 515004 Britton Fund CJD Foundation
Abstract
Objective 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.
Methods Eleven subjects were investigated at the National Prion Disease Pathology Surveillance Center for clinical, histopathological, immunohistochemical, genotypical, and PrP characteristics.
Results 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.
Interpretation 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 Digital Object Identifier (DOI)
10.1002/ana.21420 About DOI
http://www3.interscience.wiley.com/journal/119883040/abstract
Pages: 677-678 A new prionopathy Robert Will, Mark Head http://www3.interscience.wiley.com/cgi-bin/abstract/119882940/ABSTRACT
A novel human disease with abnormal prion protein sensitive to protease (prionopathy)
http://cjdmadcowbaseoct2007.blogspot.com/2008/06/novel-human-disease-with-abnormal-prion.html
re-Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease
http://betaamyloidcjd.blogspot.com/2008/04/re-association-between-deposition-of.html
Subject: Sporadic creutzfeldt-jakob disease in two adolescents (see sCJD, the big lie) Date: May 28, 2007 at 7:58 am PST
http://brain.hastypastry.net/forums/showthread.php?t=15076
http://brain.hastypastry.net/forums/archive/index.php/t-17057.html
HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/06/human-and-animal-tse-classifications-ie.html
Tuesday, June 17, 2008
Portsmouth woman did not die of mad cow-related condition, USDA says UPDATE
Updated Jun.17, 2008 08:34 KST
http://cjdmadcowbaseoct2007.blogspot.com/2008/06/portsmouth-woman-did-not-die-of-mad-cow.html
The statistical incidence of CJD cases in the United States has been revised to reflect that there is one case per 9000 in adults age 55 and older. Eighty-five percent of the cases are sporadic, meaning there is no known cause at present.
http://www.cjdfoundation.org/fact.html
see full text ;
http://prionunitusaupdate2008.blogspot.com/2008/04/progress-report-from-national-prion.html
sporadic CJD, the big lie
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0705&L=sanet-mg&T=0&P=25276
TSS