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.
DOI: 10.1002/ana.21420

Click here for Abstract.

Click here for New Scientist.

Source: BBC, New Scientist, Annals of Neurology abstract.

Written by: Catharine Paddock, PhD