Variably protease-sensitive prionopathy (VPSPr) (formerly known as Protease Sensitive Prionopathy) is a sporadic

prion protein Major prion protein (PrP), is encoded in the human by the ''PRNP'' gene also known as CD230 (cluster of differentiation 230). Expression of the protein is most predominant in the nervous system but occurs in many other tissues throughout the bod ...

disease first described in an abstract for a conference on prions in 2006, and this study was published in a 2008 report on 11 cases. The study was conducted by Gambetti P., Zou W.Q., and coworkers from the United States National Prion Disease Pathology Surveillance Center. It was first identified as a distinct disease in 2010 by Zou W.Q. and coworkers from the United States National Prion Disease Pathology Surveillance Center. VPSPr is very rare, occurring in just 2 or 3 out of every 100 million people. As of 2018, fourteen cases have been reported in the UK. It has similarities to

Creutzfeldt–Jakob disease Creutzfeldt–Jakob disease (CJD), also known as subacute spongiform encephalopathy or neurocognitive disorder due to prion disease, is an invariably fatal degenerative brain disorder. Early symptoms include memory problems, behavioral changes ...

, but clinical manifestations differ somewhat, and the abnormal

(PrP) is less resistant to digestion by proteases; some variants are more sensitive to proteases than others, hence the name: variably protease-sensitive. Patients present with behavioral and psychiatric symptoms, speech deficits (

aphasia Aphasia is an inability to comprehend or formulate language because of damage to specific brain regions. The major causes are stroke and head trauma; prevalence is hard to determine but aphasia due to stroke is estimated to be 0.1–0.4% in t ...

and/or

dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. In other words, it is a condition in which problems effectivel ...

) and progressive cognitive and motor decline (

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of t ...

parkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability. These are the four motor symptoms found in Parkinson's disease (PD), after which it is named, dementia with Lewy b ...

psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...

and

mood disorder A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the '' Diagnostic and Stati ...

). The average age at onset is 70 years, and the duration of survival is 24 months. About 40% of patients have a family history of

. Like CJD, it can be mistaken for

Alzheimer's dementia Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As t ...

. Diagnosis is difficult, as pathognomonic signs on MRI such as cortical ribboning or hockey stick sign, periodic sharp wave complexes on EEG, and tests for

14-3-3 protein 14-3-3 proteins are a family of conserved regulatory molecules that are expressed in all eukaryotic cells. 14-3-3 proteins have the ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and tran ...

and

tau protein The tau proteins (abbreviated from tubulin associated unit) are a group of six highly soluble protein isoforms produced by alternative splicing from the gene ''MAPT'' (microtubule-associated protein tau). They have roles primarily in maintaining ...

are usually not helpful, and no mutations have been observed in the coding region of the PrP gene, unlike CJD and Variant CJD. The diagnosis can be made on pathological examination. There are unique microscopic and

immunohistochemical Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to an ...

features, and the prions cannot be digested using proteases. Because 8 out of 10 patients had a positive family history of dementia in the original study, a genetic cause was suspected. Some have suggested the disease may be a sporadic form of

Gerstmann–Sträussler–Scheinker syndrome Gerstmann–Sträussler–Scheinker syndrome (GSS) is an extremely rare, usually familial, fatal neurodegenerative disease that affects patients from 20 to 60 years in age. It is exclusively heritable, and is found in only a few families all over ...

(GSS). In 2013, Zou W.Q. and coworkers revealed that the peculiar protease-resistant PrP (PrPres) originally found in VPSPr is also detectable in the brain of patients with a genetic CJD linked to PrP Valine (V) to isoleucine (I) mutation at residue 180 (PrPV180I); moreover, they found that the pathological PrP from both VPSPr and gCJDPrPV180I shares a similar glycoform-selective prion formation mechanism. ,9The authors further demonstrated that the protease-resistant PrPres from both VPSPr and gCJDV180I lacks the PrP species glycosylated at the first N-linked glycosylation site at residue 181 and they proposed that the deficiency in PrP glycosylation may be involved in the pathogenesis of the two conditions. In 2014, Gambetti P., Zou W.Q., and coworkers found that approximately 54% of mice inoculated with VPSPr brain homogenates exhibited histopathologic lesions and 34% harbored abnormal PrP similar to that of VPSPr on the first passage but no prion disease was detected on the second passage, 0suggesting that the infectivity of the pathological PrP from VPSPr is lower compared to that from the most common sporadic CJD.

References

8. Xiao X, Yuan J, Haïk S, Cali I, Zhan YA, Moudjou M, Li B, Laplanche JL, Laude H, Langeveld J, Gambetti P, Kitamoto T, Kong Q, Brandel JP, Cobb BA, Petersen RB & Zou WQ. Glycoform-selective prion formation in sporadic and familial forms of prion disease. PLoS ONE, 2013; 8:e58786. 9. Zou, WQ, Gambetti P, Xiao X, Yuan J, Langeveld J & Pirisinu L. Prions in variably protease-sensitive prionopathy: An update. Pathogens 2013; 2(3): 457-471. 10. Notari S, Xiao X, Espinosa JC, Cohen Y, Qing L, Aguilar-Calvo P, Kofskey D, Cali I, Cracco L, Kong Q, Torres JM, Zou W & Gambetti P. Transmission characteristics of variably protease-sensitive prionopathy. Emerg Infect Dis 2014, 20:2006-14.

External links

* {{Prion diseases Transmissible spongiform encephalopathies Rare diseases

See also

References

External links