Unexpected decrease of full-length prion protein in macaques inoculated with prion-contaminated blood products.

The presence of prion infectivity in the blood of patients affected by variant Creutzfeldt-Jakob disease (v-CJD), the human prion disease linked to the bovine spongiform encephalopathy (BSE), poses the risk of inter-human transmission of this fatal prion disease through transfusion. In the frame of various experiments, we have previously described that several cynomolgus macaques experimentally exposed to prion-contaminated blood products developed c-BSE/v-CJD, but the vast majority of them developed an unexpected, fatal disease phenotype focused on spinal cord involvement, which does not fulfill the classical diagnostic criteria of v-CJD. Here, we show that extensive analyses with current conventional techniques failed to detect any accumulation of abnormal prion protein (PrP) in the CNS of these myelopathic animals, i.

Non-human primates in prion diseases.

The fascinating history of prion diseases is intimately linked to the use of nonhuman primates as experimental models, which brought so fundamental and founding information about transmissibility, pathogenesis, and resistance of prions. These models are still of crucial need for risk assessment of human health and may contribute to pave a new way towards the moving field of prion-like entities which now includes the main human neurodegenerative diseases (especially Alzheimer's and Parkinson's diseases).

Phenotypic diversity of genetic Creutzfeldt-Jakob disease: a histo-molecular-based classification.

The current classification of sporadic Creutzfeldt-Jakob disease (sCJD) includes six major clinicopathological subtypes defined by the physicochemical properties of the protease-resistant core of the pathologic prion protein (PrP), defining two major PrP types (i.e., 1 and 2), and the methionine (M)/valine (V) polymorphic codon 129 of the prion protein gene (PRNP).

History of Pick's disease.

After a short summary of Arnold Pick's biography, the history of how Pick's disease (PiD) was reported is presented, from its clinical symptoms to its molecular characterization. The macroscopic description of frontotemporal atrophy by Pick is recounted followed by a description of the histological lesions observed by Alzheimer and the progressive characterization of the disease. The subsequent diagnosis has since relied on ultrastructural findings as well as immunohistochemical and biochemical techniques.

Dejerine-Roussy syndrome: Historical cases.

On June 7, 1906, Jules Dejerine (1849-1917) and Gustave Roussy (1874-1948) presented to the Société de Neurologie de Paris the first description of the thalamic syndrome with serial-section microscopic images. They also provided the first account of central poststroke pain (CPSP). They suggested that pain is one of the primary symptoms of the syndrome, although one of their own patients ("Hud") did not have pain.

Small-molecule induction of Aβ-42 peptide production in human cerebral organoids to model Alzheimer's disease associated phenotypes.

Human mini-brains (MB) are cerebral organoids that recapitulate in part the complexity of the human brain in a unique three-dimensional in vitro model, yielding discrete brain regions reminiscent of the cerebral cortex. Specific proteins linked to neurodegenerative disorders are physiologically expressed in MBs, such as APP-derived amyloids (Aβ), whose physiological and pathological roles and interactions with other proteins are not well established in humans. Here, we demonstrate that neuroectodermal organoids can be used to study the Aβ accumulation implicated in Alzheimer's disease (AD).

Unexpected prion phenotypes in experimentally transfused animals: predictive models for humans?

The recently reevaluated high prevalence of healthy carriers (1/2,000 in UK) of variant Creutzfeldt-Jakob Disease (v-CJD), whose blood might be infectious, suggests that the evolution of this prion disease might not be under full control as expected. After experimental transfusion of macaques and conventional mice with blood derived from v-CJD exposed (human and animal) individuals, we confirmed in these both models the transmissibility of v-CJD, but we also observed unexpected neurological syndromes transmissible by transfusion: despite their prion etiology confirmed through transmission experiments, these original cases would escape classical prion diagnosis, notably in the absence of detectable abnormal PrP with current techniques. It is noteworthy that macaques developed an original, yet undescribed myelopathic syndrome associating demyelination and pseudo-necrotic lesions of spinal cord, brainstem and optical tract without affecting encephalon, which is rather evocative of spinal cord disease than prion disease in human medicine.

Experimental transfusion of variant CJD-infected blood reveals previously uncharacterised prion disorder in mice and macaque.

Exposure of human populations to bovine spongiform encephalopathy through contaminated food has resulted in <250 cases of variant Creutzfeldt-Jakob disease (vCJD). However, more than 99% of vCJD infections could have remained silent suggesting a long-term risk of secondary transmission particularly through blood. Here, we present experimental evidence that transfusion in mice and non-human primates of blood products from symptomatic and non-symptomatic infected donors induces not only vCJD, but also a different class of neurological impairments.

Long-term AIDS-related PCNSL outcomes with HD-MTX and combined antiretroviral therapy.

Objective: To assess the characteristics and outcomes of patients with AIDS-related primary CNS lymphoma (AR-PCNSL) in the combined antiretroviral therapy (cART) era systematically treated with high-dose methotrexate (HD-MTX).

Methods: We retrospectively analyzed (intention-to-treat analysis) 51 consecutive patients with AR-PCNSL (median age 39 years) who were diagnosed from 1996 to 2014 and treated with a median of 6 (range 1-15) infusions of HD-MTX (3 g/m) combined with cART.

Results: Median all-patients' and survivors' follow-up lasted 23 (range 0-186) and 76 (range 23-186) months, respectively.

Wilson disease: brain pathology.

In Wilson disease (WD), brain cellular damage is thought to be due to copper deposition. Striatal lesions are the most characteristic lesions found in the brain of patients with neurologic symptoms, as emphasized in the initial reports of S.A.

Quiescin-sulfhydryl oxidase inhibits prion formation .

Prions are infectious proteins that cause a group of fatal transmissible diseases in animals and humans. The scrapie isoform (PrP) of the cellular prion protein (PrP) is the only known component of the prion. Several lines of evidence have suggested that the formation and molecular features of PrP are associated with an abnormal unfolding/refolding process.

Transmission of scrapie prions to primate after an extended silent incubation period.

Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD.

Evaluation of the protection of primates transfused with variant Creutzfeldt-Jakob disease-infected blood products filtered with prion removal devices: a 5-year update.

Background: Analysis of archived appendix samples reveals that one in 2000 individuals in the United Kingdom may carry the infectious prion protein associated with variant Creutzfeldt-Jakob disease (vCJD), raising questions about the risk of transfusion transmission from apparently healthy carriers. Blood leukoreduction shows limited efficiency against prions. Therefore, in absence of antemortem diagnostic tests, prion removal filters, including the P-Capt filter were designed to improve blood transfusion safety.

Comparative Study of Prions in Iatrogenic and Sporadic Creutzfeldt-Jakob Disease.

Differentiating iatrogenic Creutzfeldt-Jakob disease (iCJD) from sporadic CJD (sCJD) would be useful for the identification and prevention of human-to-human prion transmission. Currently, the diagnosis of iCJD depends on identification of a recognized source of contamination to which patients have been exposed, in addition to fulfilling basic requirements for the establishment of diagnosis of CJD. Attempts to identify differences in clinical manifestations, neuropathological changes and pathological prion protein (PrP) between iCJD and sCJD have been unsuccessful.

Isolated III cranial nerve palsies may point to primary histiocytic sarcoma.

Primary histiocytic sarcoma (HS) of the central nervous system (CNS) is a rare haematopoietic neoplasm. The inconsistent terminology and diagnostic criteria currently used for CNS HS have complicated the appreciation of the clinical aspects of the disease. The main differential diagnoses are non-Hodgkin's lymphoma, reactive histiocytic proliferation, dendritic cell neoplasm, undifferentiated carcinoma, inflammatory pseudotumour, Rosai-Dorfman disease and abscess.

HTLV-1-associated inflammatory myopathies: low proviral load and moderate inflammation in 13 patients from West Indies and West Africa.

Background: The Human T-cell Leukemia Virus type 1 (HTLV-1) is the causative agent of several inflammatory diseases, including HTLV-1-associated inflammatory myopathies (HAIM). Little is known about the virological and immunological characteristics of this viral disease.

Objectives: To characterize the histological and virological features of HAIM patients, in order to better understand the pathogenetic mechanisms and unravel new biological markers of this disease.

Evaluation of the zoonotic potential of transmissible mink encephalopathy.

Successful transmission of Transmissible Mink Encephalopathy (TME) to cattle supports the bovine hypothesis for the still controversial origin of TME outbreaks. Human and primate susceptibility to classical Bovine Spongiform Encephalopathy (c-BSE) and the transmissibility of L-type BSE to macaques indicate a low cattle-to-primate species barrier. We therefore evaluated the zoonotic potential of cattle-adapted TME.

Creutzfeldt-Jakob disease with unusually extensive neuropathology in a child treated with native human growth hormone.

We report a case of iatrogenic Creutzfeldt-Jakob disease(iCJD) in a child with a neonatal growth hormone (GH) deficiency that was treated with native human growth hormone (hGH) between the ages of 9 months and 7 years. Three years after the end of treatment a progressive neurological syndrome consistent with Creutzfeldt-Jakob disease (CJD) developed, leading to death within a year, at age 11. Neuropathological examination showed an unusual widespread form of CJD, notably characterized by (i) involvement of the cerebellar white matter, (ii) cortico-spinal degeneration and (iii) ballooned neurons.

Phenotype variability in progranulin mutation carriers: a clinical, neuropsychological, imaging and genetic study.

Frontotemporal dementia (FTD), characterized by behavioural and language disorders, is a clinically, genetically and pathologically heterogeneous group of diseases. The most recently identified of the four known genes is GRN, associated with 17q-linked FTD with ubiquitin-immunoreactive inclusions. GRN was analysed in 502 probands with frontal variant FTD (fvFTD), FTD with motoneuron disease (FTD-MND), primary progressive aphasia (PPA) and corticobasal degeneration syndrome (CBDS).