Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis
AbstractIn addition to motor neurone degeneration, up to 50% of amyotrophic lateral sclerosis (ALS) patients present with cognitive decline. Understanding the neurobiological changes underlying these cognitive deficits is critical, as cognitively impaired patients exhibit a shorter survival time from symptom onset. Given the pathogenic role of synapse loss in other neurodegenerative diseases in which cognitive decline is apparent, such as Alzheimer ’s disease, we aimed to assess synaptic integrity in the ALS brain. Here, we have applied a unique combination of high-resolution imaging of post-mortem tissue with neurop...
Source: Acta Neuropathologica - December 22, 2017 Category: Neurology Source Type: research

Neuronal complex I deficiency occurs throughout the Parkinson ’s disease brain, but is not associated with neurodegeneration or mitochondrial DNA damage
AbstractMitochondrial complex I deficiency occurs in the substantia nigra of individuals with Parkinson ’s disease. It is generally believed that this phenomenon is caused by accumulating mitochondrial DNA damage in neurons and that it contributes to the process of neurodegeneration. We hypothesized that if these theories are correct, complex I deficiency should extend beyond the substantia nigra to other affected brain regions in Parkinson’s disease and correlate tightly with neuronal mitochondrial DNA damage. To test our hypothesis, we employed a combination of semiquantitative immunohistochemical analyses, W...
Source: Acta Neuropathologica - December 21, 2017 Category: Neurology Source Type: research

Distinguishing features of microglia- and monocyte-derived macrophages after stroke
AbstractAfter stroke, macrophages in the ischemic brain may be derived from either resident microglia or infiltrating monocytes. Using bone marrow (BM)-chimerism and dual-reporter transgenic fate mapping, we here set out to delimit the responses of either cell type to mild brain ischemia in a mouse model of 30  min transient middle cerebral artery occlusion (MCAo). A discriminatory analysis of gene expression at 7 days post-event yielded 472 transcripts predominantly or exclusively expressed in blood-derived macrophages as well as 970 transcripts for microglia. The differentially regulated genes were fu rther col...
Source: Acta Neuropathologica - December 16, 2017 Category: Neurology Source Type: research

Spread of aggregates after olfactory bulb injection of α-synuclein fibrils is associated with early neuronal loss and is reduced long term
AbstractParkinson ’s disease is characterized by degeneration of substantia nigra dopamine neurons and by intraneuronal aggregates, primarily composed of misfolded α-synuclein. The α-synuclein aggregates in Parkinson’s patients are suggested to first appear in the olfactory bulb and enteric nerves and then prop agate, following a stereotypic pattern, via neural pathways to numerous regions across the brain. We recently demonstrated that after injection of either mouse or human α-synuclein fibrils into the olfactory bulb of wild-type mice, α-synuclein fibrils recruited endogenous α-...
Source: Acta Neuropathologica - December 5, 2017 Category: Neurology Source Type: research

Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co-localize with TDP-43 in dendrites of repeat-expanded C9orf72 amyotrophic lateral sclerosis
AbstractHexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic mechanisms are C9orf72 haploinsufficiency and/or toxicity from one or more of bi-directionally transcribed repeat RNAs and their dipeptide repeat proteins (DPRs) poly-GP, poly-GA, poly-GR, poly-PR and poly-PA. Recently, nuclear import and/or export defects especially caused by arginine-containing poly-GR or poly-PR have been proposed as significant contributors to pathogenesis based on disease models. We quantitatively studied and compared DPRs, nuclear pore prote...
Source: Acta Neuropathologica - December 1, 2017 Category: Neurology Source Type: research

Polygenic hazard score: an enrichment marker for Alzheimer ’s associated amyloid and tau deposition
AbstractThere is an urgent need for identifying nondemented individuals at the highest risk of progressing to Alzheimer ’s disease (AD) dementia. Here, we evaluated whether a recently validated polygenic hazard score (PHS) can be integrated with known in vivo cerebrospinal fluid (CSF) or positron emission tomography (PET) biomarkers of amyloid, and CSF tau pathology to prospectively predict cognitive and clinical d ecline in 347 cognitive normal (CN; baseline age range = 59.7–90.1, 98.85% white) and 599 mild cognitively impaired (MCI; baseline age range = 54.4–91.4, 98.83% white) indiv...
Source: Acta Neuropathologica - November 24, 2017 Category: Neurology Source Type: research

Neuropathology of iatrogenic Creutzfeldt –Jakob disease and immunoassay of French cadaver-sourced growth hormone batches suggest possible transmission of tauopathy and long incubation periods for the transmission of Abeta pathology
AbstractAbeta deposits and tau pathology were investigated in 24 French patients that died from iatrogenic Creutzfeldt –Jakob disease after exposure to cadaver-derived human growth hormone (c-hGH) in the 1980s. Abeta deposits were found only in one case that had experienced one of the longest incubation periods. Three cases had also intracellular tau accumulation. The analysis of 24 batches of c-hGH, produced betw een 1974 and 1988, demonstrated for the first time the presence of Abeta and tau contaminants in c-hGH (in 17 and 6 batches, respectively). The incubation of prion disease was shorter in the French patients...
Source: Acta Neuropathologica - November 22, 2017 Category: Neurology Source Type: research

The function of the cellular prion protein in health and disease
AbstractThe essential role of the cellular prion protein (PrPC) in prion disorders such as Creutzfeldt –Jakob disease is well documented. Moreover, evidence is accumulating that PrPC may act as a receptor for protein aggregates and transduce neurotoxic signals in more common neurodegenerative disorders, such as Alzheimer ’s disease. Although the pathological roles of PrPC have been thoroughly characterized, a general consensus on its physiological function within the brain has not yet been established. Knockout studies in various organisms, ranging from zebrafish to mice, have implicated PrPC in a diverse range...
Source: Acta Neuropathologica - November 18, 2017 Category: Neurology Source Type: research

Parkinson ’s disease: experimental models and reality
AbstractParkinson ’s disease (PD) is a chronic, progressive movement disorder of adults and the second most common neurodegenerative disease after Alzheimer’s disease. Neuropathologic diagnosis of PD requires moderate-to-marked neuronal loss in the ventrolateral substantia nigra pars compacta and α-synuclein (α S) Lewy body pathology. Nigrostriatal dopaminergic neurodegeneration correlates with the Parkinsonian motor features, but involvement of other peripheral and central nervous system regions leads to a wide range of non-motor features. Nigrostriatal dopaminergic neurodegeneration is shared with...
Source: Acta Neuropathologica - November 18, 2017 Category: Neurology Source Type: research

Changes in chromatin state reveal ARNT2 at a node of a tumorigenic transcription factor signature driving glioblastoma cell aggressiveness
AbstractAlthough a growing body of evidence indicates that phenotypic plasticity exhibited by glioblastoma cells plays a central role in tumor development and post-therapy recurrence, the master drivers of their aggressiveness remain elusive. Here we mapped the changes in active (H3K4me3) and repressive (H3K27me3) histone modifications accompanying the repression of glioblastoma stem-like cells tumorigenicity. Genes with changing histone marks delineated a network of transcription factors related to cancerous behavior, stem state, and neural development, highlighting a previously unsuspected association between repression ...
Source: Acta Neuropathologica - November 17, 2017 Category: Neurology Source Type: research

Co-occurrence of mixed proteinopathies in late-stage Huntington ’s disease
AbstractAccumulating evidence highlights the potential role of mixed proteinopathies (i.e., abnormal protein aggregation) in the development of clinical manifestations of neurodegenerative diseases (NDD). Huntington ’s disease (HD) is an inherited NDD caused by autosomal-dominant expanded CAG trinucleotide repeat mutation in the gene coding for Huntingtin (Htt). Previous studies have suggested the coexistence of phosphorylated-Tau, α-synuclein (α-Syn) and TAR DNA-binding protein 43 (TDP-43) inclusions in HD . However, definite evidence that HD pathology in humans can be accompanied by other proteinopathie...
Source: Acta Neuropathologica - November 13, 2017 Category: Neurology Source Type: research

Artificial intelligence in neurodegenerative disease research: use of IBM Watson to identify additional RNA-binding proteins altered in amyotrophic lateral sclerosis
AbstractAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with no effective treatments. Numerous RNA-binding proteins (RBPs) have been shown to be altered in ALS, with mutations in 11 RBPs causing familial forms of the disease, and 6 more RBPs showing abnormal expression/distribution in ALS albeit without any known mutations. RBP dysregulation is widely accepted as a contributing factor in ALS pathobiology. There are at least 1542 RBPs in the human genome; therefore, other unidentified RBPs may also be linked to the pathogenesis of ALS. We used IBM Watson® to sieve through all RBPs in the g...
Source: Acta Neuropathologica - November 13, 2017 Category: Neurology Source Type: research

Regional levels of physiological α-synuclein are directly associated with Lewy body pathology
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - November 13, 2017 Category: Neurology Source Type: research

Uncoupling N -acetylaspartate from brain pathology: implications for Canavan disease gene therapy
AbstractN-Acetylaspartate (NAA) is the second most abundant organic metabolite in the brain, but its physiological significance remains enigmatic. Toxic NAA accumulation appears to be the key factor for neurological decline in Canavan disease —a fatal neurometabolic disorder caused by deficiency in the NAA-degrading enzyme aspartoacylase. To date clinical outcome of gene replacement therapy for this spongiform leukodystrophy has not met expectations. To identify the target tissue and cells for maximum anticipated treatment benefit, we employed comprehensive phenotyping of novel mouse models to assess cell type-specif...
Source: Acta Neuropathologica - November 7, 2017 Category: Neurology Source Type: research

Cofactors influence the biological properties of infectious recombinant prions
AbstractPrion diseases are caused by a misfolding of the cellular prion protein (PrP) to a pathogenic isoform named PrPSc. Prions exist as strains, which are characterized by specific pathological and biochemical properties likely encoded in the three-dimensional structure of PrPSc. However, whether cofactors determine these different PrPSc conformations and how this relates to their specific biological properties is largely unknown. To understand how different cofactors modulate prion strain generation and selection, Protein Misfolding Cyclic Amplification was used to create a diversity of infectious recombinant prion str...
Source: Acta Neuropathologica - November 1, 2017 Category: Neurology Source Type: research

Diffuse midline gliomas with subclonal H3F3A K27M mutation and mosaic H3.3 K27M mutant protein expression
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 23, 2017 Category: Neurology Source Type: research

Multiple system atrophy: experimental models and reality
AbstractMultiple system atrophy (MSA) is a rapidly progressing fatal synucleinopathy of the aging population characterized by parkinsonism, dysautonomia, and in some cases ataxia. Unlike other synucleinopathies, in this disorder the synaptic protein, α-synuclein (α-syn), predominantly accumulates in oligodendroglial cells (and to some extent in neurons), leading to maturation defects of oligodendrocytes, demyelination, and neurodegeneration. The mechanisms through which α-syn deposits occur in oligodendrocytes and neurons in MSA are not compl etely clear. While some studies suggest that α-syn might ...
Source: Acta Neuropathologica - October 20, 2017 Category: Neurology Source Type: research

Comprehensive molecular characterisation of epilepsy-associated glioneuronal tumours
AbstractGlioneuronal tumours are an important cause of treatment-resistant epilepsy. Subtypes of tumour are often poorly discriminated by histological features and may be difficult to diagnose due to a lack of robust diagnostic tools. This is illustrated by marked variability in the reported frequencies across different epilepsy surgical series. To address this, we used DNA methylation arrays and RNA sequencing to assay the methylation and expression profiles within a large cohort of glioneuronal tumours. By adopting a class discovery approach, we were able to identify two distinct groups of glioneuronal tumour, which only...
Source: Acta Neuropathologica - October 20, 2017 Category: Neurology Source Type: research

Phenotyping cognitive impairment in dialysis patients: insights from experimental mouse models
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 20, 2017 Category: Neurology Source Type: research

Accumulation of dysfunctional SOD1 protein in Parkinson ’s disease is not associated with mutations in the SOD1 gene
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 19, 2017 Category: Neurology Source Type: research

Molecular and clinical heterogeneity of adult diffuse low-grade IDH wild-type gliomas: assessment of TERT promoter mutation and chromosome 7 and 10 copy number status allows superior prognostic stratification
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 19, 2017 Category: Neurology Source Type: research

Does Parkinson ’s disease start in the gut?
AbstractParkinson ’s disease (PD) is pathologically characterized by the presence of intraneuronal inclusions, termed Lewy bodies and Lewy neurites, whose main component is alpha-synuclein. Based on the topographic distribution of Lewy bodies and neurites established after autopsy from PD patients, Braak and cowork ers hypothesized that PD pathology may start in the gastrointestinal tract then spread through the vagus nerve to the brain. This hypothesis has been reinforced by the discovery that alpha-synuclein may be capable of spreading transcellularly, thereby providing a mechanistic basis for Braak’s hypo th...
Source: Acta Neuropathologica - October 16, 2017 Category: Neurology Source Type: research

CASQ1 mutations impair calsequestrin polymerization and cause tubular aggregate myopathy
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 16, 2017 Category: Neurology Source Type: research

Rare ADAR and RNASEH2B variants and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis
AbstractIn search of novel germline alterations predisposing to tumors, in particular to gliomas, we studied a family with two brothers affected by anaplastic gliomas, and their father and paternal great-uncle diagnosed with prostate carcinoma. In this family, whole-exome sequencing yielded rare, simultaneously heterozygous variants in the Aicardi –Goutières syndrome (AGS) genesADAR andRNASEH2B co-segregating with the tumor phenotype. AGS is a genetically induced inflammatory disease particularly of the brain, which has not been associated with a consistently increased cancer risk to date. By targeted sequenci...
Source: Acta Neuropathologica - October 13, 2017 Category: Neurology Source Type: research

DNA-methylation profiling discloses significant advantages over NanoString method for molecular classification of medulloblastoma
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 13, 2017 Category: Neurology Source Type: research

The neuroprotective transcription factor ATF5 is decreased and sequestered into polyglutamine inclusions in Huntington ’s disease
AbstractActivating transcription factor-5 (ATF5) is a stress-response transcription factor induced upon different cell stressors like fasting, amino-acid limitation, cadmium or arsenite. ATF5 is also induced, and promotes transcription of anti-apoptotic target genes likeMCL1, during the unfolded protein response (UPR) triggered by endoplasmic reticulum stress. In the brain, high ATF5 levels are found in gliomas and also in neural progenitor cells, which need to decrease their ATF5 levels for differentiation into mature neurons or glia. This initially led to believe that ATF5 is not expressed in adult neurons. More recently...
Source: Acta Neuropathologica - August 31, 2017 Category: Neurology Source Type: research

Distinct molecular profile of diffuse cerebellar gliomas
AbstractRecent studies have demonstrated that tumor-driving alterations are often different among gliomas that originated from different brain regions and have underscored the importance of analyzing molecular characteristics of gliomas stratified by brain region. Therefore, to elucidate molecular characteristics of diffuse cerebellar gliomas (DCGs), 27 adult, mostly glioblastoma cases were analyzed. Comprehensive analysis using whole-exome sequencing, RNA sequencing, and Infinium methylation array (n = 17) demonstrated their distinct molecular profile compared to gliomas in other brain regions. Frequent mutation...
Source: Acta Neuropathologica - August 29, 2017 Category: Neurology Source Type: research

MSA prions exhibit remarkable stability and resistance to inactivation
AbstractIn multiple system atrophy (MSA), progressive neurodegeneration results from the protein α-synuclein misfolding into a self-templating prion conformation that spreads throughout the brain. MSA prions are transmissible to transgenic (Tg) mice expressing mutated human α-synuclein (TgM83+/ −), inducing neurological disease following intracranial inoculation with brain homogenate from deceased patient samples. Noting the similarities between α-synuclein prions and PrP scrapie (PrPSc) prions responsible for Creutzfeldt –Jakob disease (CJD), we investigated MSA transmission under conditions ...
Source: Acta Neuropathologica - August 28, 2017 Category: Neurology Source Type: research

Linking tuberous sclerosis complex, excessive mTOR signaling, and age-related neurodegeneration: a new association between TSC1 mutation and frontotemporal dementia
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 21, 2017 Category: Neurology Source Type: research

A specific antibody to detect transcription factor T-Pit: a reliable marker of corticotroph cell differentiation and a tool to improve the classification of pituitary neuroendocrine tumours
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 19, 2017 Category: Neurology Source Type: research

The 2017 World Health Organization classification of tumors of the pituitary gland: a summary
AbstractThe 4th edition of the World Health Organization (WHO) classification of endocrine tumors has been recently released. In this new edition, major changes are recommended in several areas of the classification of tumors of the anterior pituitary gland (adenophypophysis). The scope of the present manuscript is to summarize these recommended changes, emphasizing a few significant topics. These changes include the following: (1) a novel approach for classifying pituitary neuroendocrine tumors according to pituitary adenohypophyseal cell lineages; (2) changes to the histological grading of pituitary neuroendocrine tumors...
Source: Acta Neuropathologica - August 18, 2017 Category: Neurology Source Type: research

Reduced histone H3 K27 trimethylation is encountered in about 50% of atypical teratoid/rhabdoid tumors (AT/RT) but is not associated with molecular subgroup status and outcome
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 16, 2017 Category: Neurology Source Type: research

Conserved DNA methylation combined with differential frontal cortex and cerebellar expression distinguishes C9orf72 -associated and sporadic ALS, and implicates SERPINA1 in disease
AbstractWe previously foundC9orf72-associated (c9ALS) and sporadic amyotrophic lateral sclerosis (sALS) brain transcriptomes comprise thousands of defects, among which, some are likely key contributors to ALS pathogenesis. We have now generated complementary methylome data and combine these two data sets to perform a comprehensive “multi-omic” analysis to clarify the molecular mechanisms initiating RNA misregulation in ALS. We found that c9ALS and sALS patients have generally distinct but overlapping methylome profiles, and that the c9ALS- and sALS-affected genes and pathways have similar biological functions, ...
Source: Acta Neuropathologica - August 14, 2017 Category: Neurology Source Type: research

Alpha-synuclein oligomers: a new hope
AbstractAlpha-synuclein is a protein implicated in Parkinson ’s disease and thought to be one of the main pathological drivers in the disease, although it remains unclear how this protein elicits its neurotoxic effects. Recent findings indicate that the assembly of toxic oligomeric species of alpha-synuclein may be one of the key processes for the pathology and spread of the disease. The absence of a sensitive in situ detection method has hindered the study of these oligomeric species and the role they play in the human brain until recently. In this review, we assess the evidence for the toxicity and prion-like activ...
Source: Acta Neuropathologica - August 12, 2017 Category: Neurology Source Type: research

Brainstem angiocentric gliomas with MYB –QKI rearrangements
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 12, 2017 Category: Neurology Source Type: research

Grading of diffuse astrocytic gliomas: Broders, Kernohan, Z ülch, the WHO… and Shakespeare
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 11, 2017 Category: Neurology Source Type: research

The importance of developing strain-specific models of neurodegenerative disease
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 7, 2017 Category: Neurology Source Type: research

A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8
AbstractMutations in the small heat shock protein B8 gene (HSPB8/HSP22) have been associated with distal hereditary motor neuropathy, Charcot –Marie–Tooth disease, and recently distal myopathy. It is so far not clear how mutant HSPB8 induces the neuronal and muscular phenotypes and if a common pathogenesis lies behind these diseases. Growing evidence points towards a role of HSPB8 in chaperone-associated autophagy, which has been show n to be a determinant for the clearance of poly-glutamine aggregates in neurodegenerative diseases but also for the maintenance of skeletal muscle myofibrils. To test this hypothe...
Source: Acta Neuropathologica - August 5, 2017 Category: Neurology Source Type: research

Angiocentric glioma with MYB - QKI fusion located in the brainstem, rather than cerebral cortex
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 3, 2017 Category: Neurology Source Type: research

RNAi screen identifies essential regulators of human brain metastasis-initiating cells
AbstractBrain metastases (BM) are the most common brain tumor in adults and are a leading cause of cancer mortality. Metastatic lesions contain subclones derived from their primary lesion, yet their functional characterization is limited by a paucity of preclinical models accurately recapitulating the metastatic cascade, emphasizing the need for a novel approach to BM and their treatment. We identified a unique subset of stem-like cells from primary human patient brain metastases, termed brain metastasis-initiating cells (BMICs). We now establish a BMIC patient-derived xenotransplantation (PDXT) model as an investigative t...
Source: Acta Neuropathologica - August 1, 2017 Category: Neurology Source Type: research

The choroid plexus is a key cerebral invasion route for T cells after stroke
AbstractNeuroinflammation contributes substantially to stroke pathophysiology. Cerebral invasion of peripheral leukocytes —particularly T cells—has been shown to be a key event promoting inflammatory tissue damage after stroke. While previous research has focused on the vascular invasion of T cells into the ischemic brain, the choroid plexus (ChP) as an alternative cerebral T-cell invasion route after stroke has no t been investigated. We here report specific accumulation of T cells in the peri-infarct cortex and detection of T cells as the predominant population in the ipsilateral ChP in mice as well as in hum...
Source: Acta Neuropathologica - July 31, 2017 Category: Neurology Source Type: research

Muscle satellite cells are functionally impaired in myasthenia gravis: consequences on muscle regeneration
In conclusion, the autoimmune attack in MG appears to have unsuspected pathogenic effects on SCs and muscle regeneration, with potential consequences on myogenic signalling pathways, and subsequently on clinical outcome, especially in the case of muscle stress. (Source: Acta Neuropathologica)
Source: Acta Neuropathologica - July 29, 2017 Category: Neurology Source Type: research

Persistent microglial activation and synaptic loss with behavioral abnormalities in mouse offspring exposed to CASPR2-antibodies in utero
AbstractGestational transfer of maternal antibodies against fetal neuronal proteins may be relevant to some neurodevelopmental disorders, but until recently there were no proteins identified. We recently reported a fivefold increase in CASPR2-antibodies in mid-gestation sera from mothers of children with intellectual and motor disabilities. Here, we exposed mice in utero to purified IgG from patients with CASPR2-antibodies (CASPR2-IgGs) or from healthy controls (HC-IgGs). CASPR2-IgG but not HC-IgG bound to fetal brain parenchyma, from which CASPR2-antibodies could be eluted. CASPR2-IgG exposed neonates achieved milestones ...
Source: Acta Neuropathologica - July 28, 2017 Category: Neurology Source Type: research

Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome
In conclusion, immunohistochemical evaluation of H3K27me3 global reduction is an economic, easily available and readily adaptable method for defining high-risk EPN_PFA from low-risk posterior fossa EPN_PFB tumors to inform prognosis and to enable the design of future clinical trials. (Source: Acta Neuropathologica)
Source: Acta Neuropathologica - July 21, 2017 Category: Neurology Source Type: research

Microglial-mediated PDGF-CC activation increases cerebrovascular permeability during ischemic stroke
AbstractTreatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood –brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα). However, in vitro, activation of PDGF-CC by tPA is very inefficie...
Source: Acta Neuropathologica - July 19, 2017 Category: Neurology Source Type: research

Medulloblastoma: experimental models and reality
AbstractMedulloblastoma is the most frequent malignant brain tumor in childhood, but it may also affect infants, adolescents, and young adults. Recent advances in the understanding of the disease have shed light on molecular and clinical heterogeneity, which is now reflected in the updated WHO classification of brain tumors. At the same time, it is well accepted that preclinical research and clinical trials have to be subgroup-specific. Hence, valid models have to be generated specifically for every medulloblastoma subgroup to properly mimic molecular fingerprints, clinical features, and responsiveness to targeted therapie...
Source: Acta Neuropathologica - July 19, 2017 Category: Neurology Source Type: research

α-Synuclein transfer between neurons and astrocytes indicates that astrocytes play a role in degradation rather than in spreading
AbstractRecent evidence suggests that disease progression in Parkinson ’s disease (PD) could occur by the spreading of α-synuclein (α-syn) aggregates between neurons. Here we studied the role of astrocytes in the intercellular transfer and fate of α-syn fibrils, using in vitro and ex vivo models. α-Syn fibrils can be transferred to neighboring cells; however, the transfer efficiency changes depending on the cell types. We found that α-syn is efficiently transferred from astrocytes to astrocytes and from neurons to astrocytes, but less efficiently from astrocytes to neurons. Interestingly...
Source: Acta Neuropathologica - July 19, 2017 Category: Neurology Source Type: research

Childhood white matter disorders: much more than just diseases of myelin
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - July 18, 2017 Category: Neurology Source Type: research

Affected female carriers of MTM1 mutations display a wide spectrum of clinical and pathological involvement: delineating diagnostic clues
This report should aid diagnosis and thus the clinical management and genetic counseling ofMTM1 carrier females. Furthermore, the clinical and pathological history of this cohort may be useful for therapeutic projects in males with XLMTM, as it illustrates the spectrum of possible evolution of the disease in patients surviving long term. (Source: Acta Neuropathologica)
Source: Acta Neuropathologica - July 6, 2017 Category: Neurology Source Type: research

Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood
AbstractWhereas microglia involvement in virtually all brain diseases is well accepted their role in the control of homeostasis in the central nervous system (CNS) is mainly thought to be the maintenance of neuronal function through the formation, refinement, and monitoring of synapses in both the developing and adult brain. Although the prenatal origin as well as the neuron-centered function of cortical microglia has recently been elucidated, much less is known about a distinct amoeboid microglia population formerly described as the “fountain of microglia” that appears only postnatally in myelinated regions su...
Source: Acta Neuropathologica - July 6, 2017 Category: Neurology Source Type: research