Spongiform encephalopathy in siblings with no evidence of protease-resistant prion protein or a mutation in the prion protein gene.

We discuss relevant aspects in two siblings with a neurodegenerative process of unclear aetiology who developed progressive dementia with global aphasia and hyperoral behaviour at the ages of 39 and 46 years and who died 6 and 5 years after disease onset. The cases were reported to the National Reference Center for TSE Surveillance in Göttingen, Germany. Detailed clinical examinations, CSF, blood samples, and copies of the important diagnostic tests (magnetic resonance imaging, electroencephalogram, laboratory tests) were obtained.

Report about four novel mutations in the prion protein gene.

Background/aims: Since detection of the prion protein gene (PRNP) more than 30 mutations have been discovered. Some have only been found in single case reports without known intrafamilial accumulation or neuropathological proof so that the causal connection between mutation and disease could not be proved. Those patients often present atypical clinical phenotypes, and it is not unusual that they are classified as diseases other than Creutzfeldt-Jakob disease (CJD).

Pre-progression rates in Alzheimer's disease revisited.

Background: Pre-progression rates (PPR) in Alzheimer's disease (AD) have been reported to be associated with cognitive and functional decline.

Objective: The objective was to reevaluate PPRs in a prospective cohort of AD patients.

Methods: A prospective AD cohort was analyzed.

CSF prion protein concentration and cognition in patients with Alzheimer disease.

Background/objective: PrP (c) has been suggested to play a role in AD pathophysiology. CSF concentrations of PrP (c) have been shown to be reduced in AD compared with healthy controls. Furthermore, serum levels of PrP (c) have recently been reported to be associated with the cognitive status of healthy elderly subjects.

Early detection of abnormal prion protein in genetic human prion diseases now possible using real-time QUIC assay.

Introduction: The definitive diagnosis of genetic prion diseases (gPrD) requires pathological confirmation. To date, diagnosis has relied upon the finding of the biomarkers 14-3-3 protein and total tau (t-tau) protein in the cerebrospinal fluid (CSF), but many researchers have reported that these markers are not sufficiently elevated in gPrD, especially in Gerstmann-Sträussler-Scheinker syndrome (GSS). We recently developed a new in vitro amplification technology, designated "real-time quaking-induced conversion (RT-QUIC)", to detect the abnormal form of prion protein in CSF from sporadic Creutzfeldt-Jakob disease (sCJD) patients.

Low-abundant cerebrospinal fluid proteome alterations in dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is one of the most common neurodegenerative diseases and shares multiple clinical and neuropathological parallels with Alzheimer's (AD) and Parkinson's disease (PD). A variety of clinical signs are suggestive for the diagnosis, and imaging (βCIT SPECT) contributes substantially to the diagnosis. The study reported here was performed in search for a biomarker in the cerebrospinal fluid (CSF) of these patients.

Immunotherapy in prion disease.

Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, describe a group of fatal neurodegenerative disorders affecting both humans and animals. Accumulation of misfolded prion proteins is the pathological hallmark of these disorders; such accumulation occurs in lymphoreticular tissue prior to CNS involvement in scrapie, experimental models and human variant Creutzfeldt-Jakob disease. Lymphoreticular accumulation of misfolded prion protein has not been demonstrated in human sporadic or genetic forms of TSE.

Sporadic Creutzfeldt-Jakob disease subtype-specific alterations of the brain proteome: impact on Rab3a recycling.

Sporadic Creutzfeldt-Jakob disease (sCJD) is characterized by wide clinical and pathological variability, which is mainly influenced by the conformation of the misfolded prion protein, and by the methionine and valine polymorphism at codon 129 of the prion protein gene. This heterogeneity likely implies differences in the molecular cascade that leads to the development of certain disease phenotypes. In this study, we investigated the proteome of the frontal cortex of patients with the two most common sCJD subtypes (MM1 and VV2) using 2D-DIGE and MS.

On the issue of transmissibility of Alzheimer disease: a critical review.

Results from recent experiments with rodents imply that Alzheimer disease might be inducible by seeding Aβ peptides into recipient animals. In respect to this new experimental data, public health aspects as well as epidemiological data have to be reevaluated. In this article, the available experimental and epidemiological data are reviewed.

Cerebrospinal fluid biomarker supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias: a longitudinal multicentre study over 10 years.

To date, cerebrospinal fluid analysis, particularly protein 14-3-3 testing, presents an important approach in the identification of Creutzfeldt-Jakob disease cases. However, one special point of criticism of 14-3-3 testing is the specificity in the differential diagnosis of rapid dementia. The constant observation of increased cerebrospinal fluid referrals in the national surveillance centres over the last years raises the concern of declining specificity due to higher number of cerebrospinal fluid tests performed in various neurological conditions.

Oligodendroglial process formation is differentially affected by modulating the intra- and extracellular cholesterol content.

Cholesterol is an essential component of eukaryotic plasma membranes and plays an important role in membrane organization and signaling processes. It is the major lipid component of detergent resistant caveolin-1 containing rafts which previously had been reported as a platform for nerve growth factor (NGF) signaling in oligodendrocytes (OL). Surprisingly, a knockdown of caveolin-1 attenuated the process formation of OL (Schmitz et al.

Health professions and risk of sporadic Creutzfeldt-Jakob disease, 1965 to 2010.

In 2009, a pathologist with sporadic Creutzfeldt-Jakob Disease (sCJD) was reported to the Spanish registry. This case prompted a request for information on health-related occupation in sCJD cases from countries participating in the European Creutzfeldt Jakob Disease Surveillance network (EuroCJD). Responses from registries in 21 countries revealed that of 8,321 registered cases, 65 physicians or dentists, two of whom were pathologists, and another 137 healthcare workers had been identified with sCJD.

Rapidly progressive Alzheimer's disease: a multicenter update.

The objective was to characterize a rapidly progressive subtype of Alzheimer's disease (rpAD). Multicenter (France, Germany, Japan, Spain) retrospective analyses of neuropathologically confirmed rpAD cases initially classified as prion disease due to their clinical phenotype were performed. Genetic properties, cerebrospinal fluid biomarkers, neuropathology, and clinical features were examined.

Alzheimer's disease: genetic polymorphisms and rate of decline.

Background/aim: To investigate the influence of established genetic risk factors for Alzheimer's disease on the speed of disease progression.

Methods: Polymorphisms (in ACE, ApoE, BIN1, CLU, CR1, CST3, EXOC3L2, GWA14q32.13, IL8, LDLR, PICALM, TNK1) of 40 Alzheimer's disease patients from a longitudinal study were analyzed.

Magnetic resonance imaging in E200K and V210I mutations of the prion protein gene.

Magnetic resonance imaging (MRI), with diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR), is a useful diagnostic investigation for Creutzfeldt-Jakob disease (CJD). Amendment of the diagnostic criteria for sporadic CJD (sCJD) to include defined MRI alterations has just recently been proposed. We analyzed MRI scans with FLAIR and/or DWI available of 29 patients with the E200K or the V210I mutation, and a control group of 29 sCJD patients to compare the MRI lesion profile and evaluate the applicability of new MRI criteria to genetic CJD patients.

Desmoplakin as a potential candidate for cerebrospinal fluid marker to rule out 14-3-3 false positive rates in sporadic Creutzfeldt-Jakob disease differential diagnosis.

Background: The detection of a 14-3-3 elevated level in cerebrospinal fluid (CSF) is a part of the diagnostic criteria for probable sporadic Creutzfeldt-Jakob disease (sCJD), as defined by the WHO. However, some pathological conditions associated with acute neuronal damage may result in a positive 14-3-3 test and thereby reduce test specificity in sCJD.

Objective: Desmoplakin has been previously identified as up-regulated CSF protein in sCJD and these studies aimed to investigate its diagnostic utility and compare it with two known CSF markers, 14-3-3 and tau.

Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP.

Prion diseases are fatal neurodegenerative diseases of humans and animals caused by the misfolding and aggregation of prion protein (PrP). Mammalian prion diseases are under strong genetic control but few risk factors are known aside from the PrP gene locus (PRNP). No genome-wide association study (GWAS) has been done aside from a small sample of variant Creutzfeldt-Jakob disease (CJD).

Sporadic CJD in a patient with relaplsing-remitting multiple sclerosis on an immunomodulatory treatment.

Creutzfeld-Jacob disease (CJD) is a degenerative, invariably fatal brain disorder. Multiple sclerosis (MS) is a chronic, potentially disabling, immune-mediated inflammatory demyelinating disease of the central nervous system. Here, we report a 50-year-old woman who, two years after the diagnosis of relapsing remitting MS, developed altered consciousness, dystonic posture of the left hand and myoclonic jerks.

Genome-wide study links MTMR7 gene to variant Creutzfeldt-Jakob risk.

The aim of our study was to discover genomic variations related to variant Creutzfeldt-Jakob disease (vCJD) susceptibility. A genome-wide association analysis with most vCJD samples available in the world was performed. A series of 93 vCJD UK patients and 1504 UK controls were included in the discovery stage.

Dura mater graft-associated Creutzfeldt-Jakob disease: the first case in Korea.

Since 1987, dura mater graft-associated iatrogenic Creutzfeldt-Jakob disease (dCJD) has been reported in many countries. We report the first case of dCJD in Korea. A 54-yr-old woman, who underwent resection of the meningioma in the left frontal region and received a dura mater graft 23 yr ago presented with dysesthesia followed by psychiatric symptoms and ataxia.

Rapidly progressive Alzheimer disease.

Different rates of progression have been observed among patients with Alzheimer disease. Risk factors that accelerate deterioration have been identified and some are being discussed, such as genetics, comorbidity, and the early appearance of Alzheimer disease motor signs. Progressive forms of Alzheimer disease have been reported with rapid cognitive decline and disease duration of only a few years.