2,321 results match your criteria Neuropathology and Applied Neurobiology [Journal]


Frontotemporal lobar degenerations: from basic science to clinical manifestations.

Neuropathol Appl Neurobiol 2019 Feb;45(1):3-5

Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London, UK.

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http://dx.doi.org/10.1111/nan.12537DOI Listing
February 2019

Combined FUS+ Basophilic Inclusion Body Disease and Atypical Tauopathy Presenting with an ALS/MND-plus Phenotype.

Neuropathol Appl Neurobiol 2019 Jan 19. Epub 2019 Jan 19.

Sheffield Institute for Translational Neuroscience, University of Sheffield, UK.

Aims: Amyotrophic lateral sclerosis / motor neurone disease (ALS/MND) is characterised by the presence of inclusions containing TDP-43 within motor neurones. In rare cases, ALS/MND may be associated with inclusions containing other proteins, such as fused in sarcoma (FUS), whilst motor system pathology may rarely be a feature of other neurodegenerative disorders. We here have investigated the association of FUS and tau pathology. Read More

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http://dx.doi.org/10.1111/nan.12542DOI Listing
January 2019
3 Reads

Long non-coding RNAs: important regulators in the development, function, and disorders of the central nervous system.

Neuropathol Appl Neurobiol 2019 Jan 13. Epub 2019 Jan 13.

The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.

Genome-wide transcriptional studies have demonstrated that tens of thousands of lncRNA genes are expressed in the CNS and that they exhibit tissue- and cell-type specificity. Their regulated and dynamic expression, and their co-expression with protein-coding gene neighbours, have led to the study of the functions of lncRNAs in CNS development and disorders. In this review, we describe the general characteristics, localization, and classification of lncRNAs. Read More

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http://dx.doi.org/10.1111/nan.12541DOI Listing
January 2019
1 Read

Spatiotemporal dynamics of PDGFRβ expression in pericytes and glial scar formation in penetrating brain injuries in adults.

Neuropathol Appl Neurobiol 2019 Jan 12. Epub 2019 Jan 12.

Department of Clinical and Experimental Epilepsy, Queen Square, London.

Aims: Understanding the spatiotemporal dynamics of reactive cell types following brain injury is important for future therapeutic interventions. We have previously used penetrating cortical injuries following intracranial recordings as a brain repair model to study scar-forming nestin-expressing cells. We now explore the relationship between nestin-expressing cells, PDGFRβ pericytes and Olig2 glia, including their proliferation and functional maturation. Read More

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http://dx.doi.org/10.1111/nan.12539DOI Listing
January 2019

Investigating ARSACS: models for understanding cerebellar degeneration.

Neuropathol Appl Neurobiol 2019 Jan 12. Epub 2019 Jan 12.

Stem Cells Therapies in Neurodegenerative Diseases Lab, Research Center "Principe Felipe", Valencia, Spain.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease that includes progressive cerebellar dysfunction. ARSACS is caused by an autosomal recessive loss-of-function mutation in the SACS gene, which encodes for SACSIN. Although animal models are still necessary to investigate the role of SACSIN in the pathology of this disease, more reliable human cellular models need to be generated to better understand the cerebellar pathophysiology of ARSACS. Read More

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http://dx.doi.org/10.1111/nan.12540DOI Listing
January 2019

Review: PrP 106-126 - 25 years after.

Neuropathol Appl Neurobiol 2019 Jan 12. Epub 2019 Jan 12.

Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy.

A quarter of a century ago, we proposed an innovative approach to study the pathogenesis of prion disease, one of the most intriguing biomedical problems that remains unresolved. The synthesis of a peptide homologous to residues 106-126 of the human prion protein (PrP106-126), a sequence present in the PrP amyloid protein of Gerstmann-Sträussler-Scheinker syndrome patients, provided a tractable tool for investigating the mechanisms of neurotoxicity. Together with several other discoveries at the beginning of the 1990s, PrP106-126 contributed to underpin the role of amyloid in the pathogenesis of protein-misfolding neurodegenerative disorders. Read More

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http://dx.doi.org/10.1111/nan.12538DOI Listing
January 2019
1 Read

Review: Clinical, genetic and neuroimaging features of frontotemporal dementia.

Neuropathol Appl Neurobiol 2019 Feb;45(1):6-18

Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.

Frontotemporal dementia (FTD) is a heterogeneous group of disorders causing neurodegeneration within a network of areas centred on the frontal and temporal lobes. Clinically, patients present with behavioural symptoms (behavioural variant FTD) or language disturbance (primary progressive aphasia), although there is an overlap with motor neurone disease and atypical parkinsonian disorders. Whilst neuroimaging commonly reveals abnormalities in the frontal and temporal lobes, a closer review identifies a more complex picture with variable asymmetry of neuronal loss, widespread subcortical involvement and in many cases more posterior cortical atrophy. Read More

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http://doi.wiley.com/10.1111/nan.12535
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http://dx.doi.org/10.1111/nan.12535DOI Listing
February 2019
7 Reads

Review: Modelling the pathology and behaviour of frontotemporal dementia.

Neuropathol Appl Neurobiol 2019 Feb;45(1):58-80

UK Dementia Research Institute, King's College London, London, Camberwell, UK.

Frontotemporal dementia (FTD) encompasses a collection of clinically and pathologically diverse neurological disorders. Clinical features of behavioural and language dysfunction are associated with neurodegeneration, predominantly of frontal and temporal cortices. Over the past decade, there have been significant advances in the understanding of the genetic aetiology and neuropathology of FTD which have led to the creation of various disease models to investigate the molecular pathways that contribute to disease pathogenesis. Read More

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http://dx.doi.org/10.1111/nan.12536DOI Listing
February 2019
1 Read

Review: Molecular pathology of frontotemporal lobar degenerations.

Neuropathol Appl Neurobiol 2019 Feb;45(1):41-57

International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.

Frontotemporal lobar degeneration (FTLD) is a group of disorders that principally affect the frontal and temporal lobes of the brain. In many parts of the world, FTLD is rapidly becoming a serious health burden on society and, as a result, the molecular mechanisms that underlie its onset and development have been the target of intense research efforts in recent years. Nonetheless, despite crucial pathological and genetic discoveries in this area much is still uncertain about how the many genes associated with this disease cause the observed neurodegeneration. Read More

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http://dx.doi.org/10.1111/nan.12534DOI Listing
February 2019

Chemicals, somatic mutations and neurodegeneration: evidence from Western Pacific amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC): Commentary on: Leija-Salazar M, Piette C, Proukakis C. Review: Somatic mutations in neurodegeneration. Neuropathol Appl Neurobiol 2018; 44: 267-85.

Authors:
P S Spencer G Kisby

Neuropathol Appl Neurobiol 2018 Dec 17. Epub 2018 Dec 17.

Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific Northwest (COMP-N), Western University of Health Sciences, Lebanon, OR, USA.

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http://doi.wiley.com/10.1111/nan.12533
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http://dx.doi.org/10.1111/nan.12533DOI Listing
December 2018
1 Read

MiR-16-5p is frequently down-regulated in astrocytic gliomas and modulates glioma cell proliferation, apoptosis, and response to cytotoxic therapy.

Neuropathol Appl Neurobiol 2018 Dec 13. Epub 2018 Dec 13.

Department of Neuropathology, Heinrich Heine University, Düsseldorf, Germany.

Aims: Aberrant expression of microRNAs (miRNAs) is frequent in various cancers including gliomas. We aimed to characterize the role of miR-16-5p as a candidate tumour suppressor miRNA in gliomas.

Methods: Real-time PCR-based approaches were used for miRNA and mRNA expression profiling of glioma and non-neoplastic brain tissues as well as glioma cell lines. Read More

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http://dx.doi.org/10.1111/nan.12532DOI Listing
December 2018

Age-associated changes in the blood-brain barrier: comparative studies in human and mouse.

Authors:

Neuropathol Appl Neurobiol 2018 12;44(7):747-748

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http://dx.doi.org/10.1111/nan.12515DOI Listing
December 2018

Heterogeneity in α-synuclein subtypes and their expression in cortical brain tissue lysates from Lewy body diseases and Alzheimer's disease.

Neuropathol Appl Neurobiol 2018 Nov 13. Epub 2018 Nov 13.

Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar.

Aims: Lewy body diseases are neuropathologically characterized by the abnormal accumulation of α-synuclein (α-syn) protein within vulnerable neurons. Although studies have evaluated α-syn in post mortem brain tissue, previous findings have been limited by typically employing pan-α-syn antibodies that may not recognize disease-relevant forms of protein. We investigated the presence of α-syn species present in post mortem brain tissues from Lewy body disease and Alzheimer's disease. Read More

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http://dx.doi.org/10.1111/nan.12531DOI Listing
November 2018
7 Reads

Review: Fluid biomarkers for frontotemporal dementias.

Neuropathol Appl Neurobiol 2019 Feb 3;45(1):81-87. Epub 2018 Dec 3.

Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London, UK.

Frontotemporal dementias (FTDs) are clinically, genetically and pathologically heterogeneous neurodegenerative disorders that affect the frontal and anterior temporal lobes of the brain. They are relatively common causes of young-onset dementia and usually present with behavioural disturbance (behavioural variant FTD) or language impairment (primary progressive aphasia), but there is also overlap with motor neurone disease and the atypical parkinsonian disorders, corticobasal syndrome and progressive supranuclear palsy. At post mortem, neuronal inclusions containing tau, TDP-43 or infrequently FUS protein are seen in most cases. Read More

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http://doi.wiley.com/10.1111/nan.12530
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http://dx.doi.org/10.1111/nan.12530DOI Listing
February 2019
10 Reads

Invited Review: APOE at the interface of inflammation, neurodegeneration and pathological protein spread in Alzheimer's disease.

Neuropathol Appl Neurobiol 2018 Nov 5. Epub 2018 Nov 5.

UK Dementia Research Institute and Centre for Discovery Brain Sciences, The University of Edinburgh, Edinburgh, UK.

Despite more than a century of research, the aetiology of sporadic Alzheimer's disease (AD) remains unclear and finding disease modifying treatments for AD presents one of the biggest medical challenges of our time. AD pathology is characterized by deposits of aggregated amyloid beta (Aβ) in amyloid plaques and aggregated tau in neurofibrillary tangles. These aggregates begin in distinct brain regions and spread throughout the brain in stereotypical patterns. Read More

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http://dx.doi.org/10.1111/nan.12529DOI Listing
November 2018
13 Reads

Histological heterogeneity in a large clinical cohort of juvenile idiopathic inflammatory myopathy: analysis by myositis autoantibody and pathological features.

Neuropathol Appl Neurobiol 2018 Oct 31. Epub 2018 Oct 31.

Developmental Biology of Birth Defects, Developmental Biology and Cancer Programme, UCL GOS Institute of Child Health, UCL London, UK.

Aim: Juvenile idiopathic inflammatory myopathies (IIM) have been recently reclassified into clinico-serological subgroups. Myopathological correlates of the subgroups are incompletely understood.

Methods: We studied muscle biopsies from 101 children with clinically and serologically-defined juvenile IIM from the UK JDM Cohort and Biomarker Study by applying the international JDM score tool, myopathological review, and C5b-9 complement analysis. Read More

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http://doi.wiley.com/10.1111/nan.12528
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http://dx.doi.org/10.1111/nan.12528DOI Listing
October 2018
4 Reads

Does ALS-FUS without FUS mutation represent ALS-FET? Report of three cases.

Neuropathol Appl Neurobiol 2018 Oct 29. Epub 2018 Oct 29.

Neurological Tissue Bank of the Biobanc-Hospital Clínic-IDIBAPS, Barcelona, Spain.

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http://doi.wiley.com/10.1111/nan.12527
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http://dx.doi.org/10.1111/nan.12527DOI Listing
October 2018
3 Reads

Review: Neuropathology of non-tau frontotemporal lobar degeneration.

Neuropathol Appl Neurobiol 2019 Feb;45(1):19-40

Department of Pathology, University of British Columbia and Vancouver General Hospital, Vancouver, BC, Canada.

Frontotemporal dementia (FTD) is a heterogeneous clinical syndrome associated with frontotemporal lobar degeneration (FTLD) as a relatively consistent neuropathological hallmark feature. However, the discoveries in the past decade of many of the relevant pathological proteins aggregating in human FTD brains in addition to several new FTD causing gene mutations underlined that FTD is a diverse condition on the neuropathological and genetic basis. This resulted in a novel molecular classification of these conditions based on the predominant protein abnormality and allows most cases of FTD to be placed now into one of three broad molecular subgroups; FTLD with tau, TAR DNA-binding protein 43 or FET protein accumulation (FTLD-tau, FTLD-TDP and FTLD-FET respectively). Read More

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http://dx.doi.org/10.1111/nan.12526DOI Listing
February 2019
2 Reads

Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes.

Neuropathol Appl Neurobiol 2018 Oct 22. Epub 2018 Oct 22.

Department of Pathology, Amsterdam Neuroscience, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands.

Aims: Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by progressive loss of motor neurons, muscle weakness, spasticity, paralysis and death usually within 2-5 years of onset. Neuroinflammation is a hallmark of ALS pathology characterized by activation of glial cells, which respond by upregulating small heat shock proteins (HSPBs), but the exact underlying pathological mechanisms are still largely unknown. Here, we investigated the association between ALS disease duration, lower motor neuron loss, TARDNA-binding protein 43 (TDP-43) pathology, neuroinflammation and HSPB expression. Read More

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http://dx.doi.org/10.1111/nan.12525DOI Listing
October 2018
3 Reads

Baseline concentration of misfolded α-synuclein aggregates in cerebrospinal fluid predicts risk of cognitive decline in Parkinson's disease.

Neuropathol Appl Neurobiol 2018 Oct 22. Epub 2018 Oct 22.

Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: The prognostic significance of misfolded α-synuclein (α-Syn) aggregates in Parkinson's disease (PD) has not been well investigated. The aim of this study was to reveal the relationship between misfolded α-Syn aggregate concentration in cerebrospinal fluid (CSF) and cognitive decline risk in PD.

Methods: A total of 278 patients with PD were retrospectively included. Read More

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http://dx.doi.org/10.1111/nan.12524DOI Listing
October 2018
1 Read

Integrated molecular characterization of IDH-mutant glioblastomas.

Neuropathol Appl Neurobiol 2018 Oct 16. Epub 2018 Oct 16.

Department of Neuropathology, University Hospital Heidelberg, Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Aims: Mutations of isocitrate dehydrogenase (IDH)1/2 affect almost all astrocytomas of WHO grade II and III. A subset of IDH-mutant astrocytic tumours progresses to IDH-mutant glioblastoma or presents with the histology of a glioblastoma at first presentation. We set out here to assess the molecular spectrum of IDH-mutant glioblastomas. Read More

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http://doi.wiley.com/10.1111/nan.12523
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http://dx.doi.org/10.1111/nan.12523DOI Listing
October 2018
2 Reads

Review: Challenges in the histopathological classification of ganglioglioma and DNT: microscopic agreement studies and a preliminary genotype-phenotype analysis.

Neuropathol Appl Neurobiol 2018 Oct 16. Epub 2018 Oct 16.

Department of Clinical and Experimental Epilepsy UCL Queens Square, Institute of Neurology, London.

Low-grade epilepsy-associated brain tumours (LEAT) are the second most common cause for drug-resistant, focal epilepsy, that is ganglioglioma (GG) and dysembryoplastic neuroepithelial tumours (DNT). However, molecular pathogenesis, risk factors for malignant progression and their frequent association with drug-resistant focal seizures remain poorly understood. This contrasts recent progress in understanding the molecular-genetic basis and targeted treatment options in diffuse gliomas. Read More

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http://doi.wiley.com/10.1111/nan.12522
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http://dx.doi.org/10.1111/nan.12522DOI Listing
October 2018
7 Reads

IDH mutant astrocytoma: biomarkers for prognostic stratification and the next frontiers.

Neuropathol Appl Neurobiol 2018 Oct 16. Epub 2018 Oct 16.

Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.1111/nan.12521DOI Listing
October 2018
3 Reads

Invited Review: From nose to gut - the role of the microbiome in neurological disease.

Neuropathol Appl Neurobiol 2018 Oct 8. Epub 2018 Oct 8.

Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.

Inflammation and neurodegeneration are key features of many chronic neurological diseases, yet the causative mechanisms underlying these processes are poorly understood. There has been mounting interest in the role of the human microbiome in modulating the inflammatory milieu of the central nervous system (CNS) in health and disease. To date, most research has focussed on a gut-brain axis, with other mucosal surfaces being relatively neglected. Read More

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http://doi.wiley.com/10.1111/nan.12520
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http://dx.doi.org/10.1111/nan.12520DOI Listing
October 2018
4 Reads

Diagnostic potential of sarcoplasmic MxA expression in subsets of dermatomyositis.

Neuropathol Appl Neurobiol 2018 Sep 28. Epub 2018 Sep 28.

Department of Internal Medicine and Clinical Immunology, Paris-Sorbonne University, Public Assistance-Hospitals of Paris (APHP), Pitié-Salpêtrière University Hospital, INSERM, UMR974, Inflammation-Immunopathology-Biotherapy Department (DHU I2B), and Reference Center for Neuromuscular Pathologies, Institute of Myology, Paris, France.

Aims: To elucidate the diagnostic value of sarcoplasmic expression of myxovirus resistance protein A (MxA) for dermatomyositis (DM) specifically analyzing different DM subforms, and to test the superiority of MxA to other markers.

Methods: Immunohistochemistry for MxA and retinoic acid-inducible gene I (RIG-I) was performed on skeletal muscle samples and compared with the item presence of perifascicular atrophy (PFA) in 57 DM patients with anti-Mi-2 (n=6), -TIF1-γ (n=10), -NXP2 (n=13), -MDA5 (n=10), or -SAE (n=1) autoantibodies and with no detectable autoantibody (n=17). Among the patients, 9 suffered from cancer and 22 were juvenile-onset type. Read More

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http://dx.doi.org/10.1111/nan.12519DOI Listing
September 2018
9 Reads
3.930 Impact Factor

HDAC2 dysregulation in the nucleus basalis of Meynert during the progression of Alzheimer's disease.

Neuropathol Appl Neurobiol 2018 Sep 25. Epub 2018 Sep 25.

Department of Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.

Aims: Alzheimer's disease (AD) is characterized by degeneration of cholinergic basal forebrain (CBF) neurons in the nucleus basalis of Meynert (nbM), which provides the major cholinergic input to the cortical mantle and is related to cognitive decline in patients with AD. Cortical histone deacetylase (HDAC) dysregulation has been associated with neuronal degeneration during AD progression. However, whether HDAC alterations play a role in CBF degeneration during AD onset is unknown. Read More

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http://dx.doi.org/10.1111/nan.12518DOI Listing
September 2018
3.930 Impact Factor

Is APOE ε4 required for Alzheimer's disease to develop in TREM2 p.R47H variant carriers?

Neuropathol Appl Neurobiol 2018 Sep 19. Epub 2018 Sep 19.

UK Dementia Research Institute at UCL (UK DRI), London, UK.

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http://dx.doi.org/10.1111/nan.12517DOI Listing
September 2018
5 Reads

Imbalances in protein homeostasis caused by mutant desmin.

Neuropathol Appl Neurobiol 2018 Sep 4. Epub 2018 Sep 4.

Institute of Neuropathology, University Hospital Erlangen, Erlangen, Germany.

Aims: We investigated newly generated immortalized heterozygous and homozygous R349P desmin knock-in myoblasts in conjunction with the corresponding desminopathy mice as models for desminopathies to analyse major protein quality control processes in response to the presence of R349P mutant desmin.

Methods: We used hetero- and homozygous R349P desmin knock-in mice for analyses and for crossbreeding with p53 knock-out mice to generate immortalized R349P desmin knock-in skeletal muscle myoblasts and myotubes. Skeletal muscle sections and cultured muscle cells were investigated by indirect immunofluorescence microscopy, proteasomal activity measurements and immunoblotting addressing autophagy rate, chaperone-assisted selective autophagy and heat shock protein levels. Read More

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http://doi.wiley.com/10.1111/nan.12516
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http://dx.doi.org/10.1111/nan.12516DOI Listing
September 2018
11 Reads

SIRT1 is increased in affected brain regions and hypothalamic metabolic pathways are altered in Huntington disease.

Neuropathol Appl Neurobiol 2018 Jul 18. Epub 2018 Jul 18.

Translational Neuroendocrine Research Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.

Aims: Metabolic dysfunction is involved in modulating the disease process in Huntington disease (HD) but the underlying mechanisms are not known. The aim of this study was to investigate if the metabolic regulators sirtuins are affected in HD.

Methods: Quantitative real-time polymerase chain reactions were used to assess levels of SIRT1-3 and downstream targets in post mortem brain tissue from HD patients and control cases as well as after selective hypothalamic expression of mutant huntingtin (HTT) using recombinant adeno-associated viral vectors in mice. Read More

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http://dx.doi.org/10.1111/nan.12514DOI Listing
July 2018
1 Read

Review: Revisiting the human cholinergic nucleus of the diagonal band of Broca.

Neuropathol Appl Neurobiol 2018 12 13;44(7):647-662. Epub 2018 Aug 13.

Neuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.

Although the nucleus of the vertical limb of the diagonal band of Broca (nvlDBB) is the second largest cholinergic nucleus in the basal forebrain, after the nucleus basalis of Meynert, it has not generally been a focus for studies of neurodegenerative disorders. However, the nvlDBB has an important projection to the hippocampus and discrete lesions of the rostral basal forebrain have been shown to disrupt retrieval memory function, a major deficit seen in patients with Lewy body disorders. One reason for its neglect is that the anatomical boundaries of the nvlDBB are ill defined and this area of the brain is not part of routine diagnostic sampling protocols. Read More

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http://dx.doi.org/10.1111/nan.12513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282557PMC
December 2018
9 Reads

Exploring the putative role of kallikrein-6, calpain-1 and cathepsin-D in the proteolytic degradation of α-synuclein in multiple system atrophy.

Neuropathol Appl Neurobiol 2018 Jul 11. Epub 2018 Jul 11.

Queen Square Brain Bank, UCL Institute of Neurology, University College London, London, UK.

Aims: There is evidence that accumulation of α-synuclein (α-syn) in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) results from impaired removal of α-syn rather than its overproduction. Kallikrein-6 (KLK6), calpain-1 (CAPN1) and cathepsin-D (CTSD) are among a small number of proteases that cleave α-syn and are dysregulated in PD and DLB. Our aim in this study was to determine whether protease activity is altered in another α-synucleinopathy, multiple system atrophy (MSA), and might thereby modulate the regional distribution of α-syn accumulation. Read More

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http://dx.doi.org/10.1111/nan.12512DOI Listing
July 2018
4 Reads

Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with Amyotrophic Lateral Sclerosis.

Neuropathol Appl Neurobiol 2018 Jun 16. Epub 2018 Jun 16.

Laboratory for Molecular Neurobiomarker Research, Department of Neurosciences, KU Leuven, Leuven, Belgium.

Aims: Amyotrophic lateral sclerosis (ALS) is the most common motor neuron degeneration disease with a diagnostic delay of about 1 year after symptoms onset. In ALS, blood neurofilament light chain (NfL) levels are elevated, but it is not entirely clear what drives this increase and what the diagnostic performance of serum NfL is in terms of predictive values and likelihood ratios. The aims of this study were to further explore the prognostic and diagnostic performances of serum NfL to discriminate between patients with ALS and ALS mimics, and to investigate the relationship between serum NfL with motor neuron degeneration. Read More

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http://dx.doi.org/10.1111/nan.12511DOI Listing
June 2018
9 Reads

Pro-inflammatory activation of microglia in the brain of patients with sepsis.

Neuropathol Appl Neurobiol 2018 May 27. Epub 2018 May 27.

Center for Brain Research, Medical University of Vienna, Vienna, Austria.

Aims: Experimental data suggest that systemic immune activation may create a pro-inflammatory environment with microglia activation in the central nervous system in the absence of overt inflammation, which in turn may be deleterious in conditions of neurodegenerative disease. The extent to which this is relevant for the human brain is unknown. The central aim of this study is to provide an in-depth characterization of the microglia and macrophage response to systemic inflammation. Read More

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http://dx.doi.org/10.1111/nan.12502DOI Listing

CDKN2A/B Loss Is Associated with Anaplastic Transformation in a Case of NTRK2 Fusion-positive Pilocytic Astrocytoma.

Neuropathol Appl Neurobiol 2018 May 27. Epub 2018 May 27.

Department of Pathology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

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http://doi.wiley.com/10.1111/nan.12503
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http://dx.doi.org/10.1111/nan.12503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258357PMC
May 2018
2 Reads

Differential insular cortex subregional vulnerability to α-synuclein pathology in Parkinson's disease and dementia with Lewy bodies.

Neuropathol Appl Neurobiol 2018 May 24. Epub 2018 May 24.

Section Clinical Neuroanatomy, Department of Anatomy and Neurosciences, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.

Aim: The insular cortex consists of a heterogenous cytoarchitecture and diverse connections and is thought to integrate autonomic, cognitive, emotional and interoceptive functions to guide behaviour. In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), it reveals α-synuclein pathology in advanced stages. The aim of this study is to assess the insular cortex cellular and subregional vulnerability to α-synuclein pathology in well-characterized PD and DLB subjects. Read More

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http://dx.doi.org/10.1111/nan.12501DOI Listing
May 2018
4 Reads

The role of lysosomes and autophagosomes in frontotemporal lobar degeneration.

Neuropathol Appl Neurobiol 2018 May 23. Epub 2018 May 23.

Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Salford Royal Hospital, Salford, UK.

Introduction: Cell biological and genetic evidence implicate failures in degrading aggregating proteins, such as tau and TDP-43, through the autophagy or lysosomal pathways in the pathogenesis of frontotemporal lobar degeneration (FTLD).

Methods: We investigated changes in the degradative pathways in 60 patients with different pathological or genetic forms of FTLD employing immunohistochemistry for marker proteins such as lysosomal-associated membrane proteins 1 (LAMP-1) and 2 (LAMP-2), cathepsin D (CTSD) and microtubule-associated protein 1 light chain 3 alpha (LC3A). Immunostained sections were qualitatively and semi-quantitatively assessed for the appearance, distribution and intensity of staining in neurones of the dentate gyrus (DG) and CA4 region of the hippocampus, and the temporal cortex (Tcx). Read More

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http://dx.doi.org/10.1111/nan.12500DOI Listing
May 2018
12 Reads

Expression of myxovirus-resistance protein A: a possible marker of muscle disease activity and autoantibody specificities in juvenile dermatomyositis.

Neuropathol Appl Neurobiol 2018 May 16. Epub 2018 May 16.

Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK.

Aims: To evaluate the relationship between expression of myxovirus-resistance protein A (MxA) protein on muscle biopsies by immunohistochemistry and disease activity in juvenile dermatomyositis (JDM) patients. Also, another aim was to investigate whether the expression of MxA is related with myositis-specific autoantibodies (MSA) status in JDM patients.

Methods: 103 patients (median aged 6. Read More

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http://dx.doi.org/10.1111/nan.12498DOI Listing
May 2018
6 Reads

Season of death and nigral neuronal density in a high-latitude region.

Neuropathol Appl Neurobiol 2018 May 12. Epub 2018 May 12.

Department of Neurology, University of Turku, Turku, Finland.

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http://dx.doi.org/10.1111/nan.12496DOI Listing
May 2018
2 Reads

Pathoarchitectonics of the cerebral cortex in chorea-acanthocytosis and Huntington's disease.

Neuropathol Appl Neurobiol 2018 May 2. Epub 2018 May 2.

Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität München, München, Germany.

Aims: Quantitative estimation of cortical neurone loss in cases with chorea-acanthocytosis (ChAc) and its impact on laminar composition.

Methods: We used unbiased stereological tools to estimate the degree of cortical pathology in serial gallocyanin-stained brain sections through the complete hemispheres of three subjects with genetically verified ChAc and a range of disease durations. We compared these results with our previous data of five Huntington's disease (HD) and five control cases. Read More

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http://dx.doi.org/10.1111/nan.12495DOI Listing
May 2018
16 Reads

Molecular characteristics of multifocal brain histiocytic sarcoma.

Neuropathol Appl Neurobiol 2018 Apr 21. Epub 2018 Apr 21.

Department of Pathology, UNIROUEN, INSERM U1245, Rouen University Hospital, Normandie Université, Rouen, France.

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http://dx.doi.org/10.1111/nan.12490DOI Listing
April 2018
4 Reads

Down-regulation of natural resistance-associated macrophage protein-1 (Nramp1) is associated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP )-induced α-synuclein accumulation and neurotoxicity.

Neuropathol Appl Neurobiol 2018 Apr 21. Epub 2018 Apr 21.

School of Pharmacy, National Taiwan University, Taipei, Taiwan.

Aims: The accumulation of α-synuclein is a hallmark in the pathogenesis of Parkinson's disease (PD). Natural resistance-associated macrophage protein-1 (Nramp1) was previously shown to contribute to the degradation of extracellular α-synuclein in microglia under conditions of iron overload. This study was aimed at investigating the role of Nramp1 in α-synuclein pathology in the neurone under 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP ) treatment. Read More

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http://dx.doi.org/10.1111/nan.12493DOI Listing
April 2018
38 Reads

A nonmyeloablative chimeric mouse model accurately defines microglia and macrophage contribution in glioma.

Neuropathol Appl Neurobiol 2018 Apr 20. Epub 2018 Apr 20.

Stem Cell and Neurotherapies Laboratory, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.

Aims: Resident and peripherally derived glioma associated microglia/macrophages (GAMM) play a key role in driving tumour progression, angiogenesis, invasion and attenuating host immune responses. Differentiating these cells' origins is challenging and current preclinical models such as irradiation-based adoptive transfer, parabiosis and transgenic mice have limitations. We aimed to develop a novel nonmyeloablative transplantation (NMT) mouse model that permits high levels of peripheral chimerism without blood-brain barrier (BBB) damage or brain infiltration prior to tumour implantation. Read More

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http://doi.wiley.com/10.1111/nan.12489
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http://dx.doi.org/10.1111/nan.12489DOI Listing
April 2018
8 Reads

Prominent microglial activation in cortical white matter is selectively associated with cortical atrophy in primary progressive aphasia.

Neuropathol Appl Neurobiol 2018 Apr 21. Epub 2018 Apr 21.

Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Aims: Primary progressive aphasia (PPA) is a clinical syndrome characterized by selective language impairments associated with focal cortical atrophy favouring the language dominant hemisphere. PPA is associated with Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and significant accumulation of activated microglia. Activated microglia can initiate an inflammatory cascade that may contribute to neurodegeneration, but their quantitative distribution in cortical white matter and their relationship with cortical atrophy remain unknown. Read More

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http://dx.doi.org/10.1111/nan.12494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196127PMC
April 2018
5 Reads

Paraneoplastic cerebellar degeneration: Yo antibody alters mitochondrial calcium buffering capacity.

Neuropathol Appl Neurobiol 2018 Apr 21. Epub 2018 Apr 21.

Department of Neurology, Haukeland University Hospital, Bergen, Norway.

Aim: Neurodegeneration is associated with dysfunction of calcium buffering capacity and thereby sustained cellular and mitochondrial calcium overload. Paraneoplastic cerebellar degeneration (PCD), characterized by progressive Purkinje neurone degeneration following paraneoplastic Yo antibody internalization and binding to cerebellar degeneration-related protein CDR2 and CDR2L, has been linked to intracellular calcium homeostasis imbalance due to calbindin D malfunction. Therefore, we hypothesized that Yo antibody internalization affects not only calbindin calcium binding capacity, but also calcium-sensitive mitochondrial-associated signalling, causing mitochondrial calcium overload and thereby Purkinje neurone death. Read More

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http://dx.doi.org/10.1111/nan.12492DOI Listing
April 2018
8 Reads

Fitting the epigenome into the picture: methylation classification for paediatric brain tumours.

Neuropathol Appl Neurobiol 2018 10;44(6):543-547

Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.

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http://dx.doi.org/10.1111/nan.12488DOI Listing
October 2018
3 Reads

Detection of alpha-synuclein conformational variants from gastro-intestinal biopsy tissue as a potential biomarker for Parkinson's disease.

Neuropathol Appl Neurobiol 2018 12 8;44(7):722-736. Epub 2018 May 8.

Oxford Parkinson's Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.

Aims: Gastrointestinal (GI) α-synuclein (aSyn) detection as a potential biomarker of Parkinson's disease (PD) is challenged by conflicting results of recent studies. To increase sensitivity and specificity, we applied three techniques to detect different conformations of aSyn in GI biopsies obtained from a longitudinal, clinically well-characterized cohort of PD patients and healthy controls (HC).

Methods: With immunohistochemistry (IHC), we used antibodies reactive for total, phosphorylated and oligomeric aSyn; with aSyn proximity ligation assay (AS-PLA), we targeted oligomeric aSyn species specifically; and with paraffin-embedded tissue blot (AS-PET-blot) we aimed to detect fibrillary, synaptic aSyn. Read More

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http://dx.doi.org/10.1111/nan.12486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282510PMC
December 2018
6 Reads

Genomic profiling of anaplastic meningioma identifies recurrent genetic alterations with relevance to lower-grade meningioma.

Neuropathol Appl Neurobiol 2018 Apr 19. Epub 2018 Apr 19.

Department of Neurological Surgery, University of Washington School of Medicine, Seattle, WA, USA.

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http://dx.doi.org/10.1111/nan.12487DOI Listing
April 2018
4 Reads

TDP-43 pathology in multiple system atrophy: colocalization of TDP-43 and α-synuclein in glial cytoplasmic inclusions.

Neuropathol Appl Neurobiol 2018 12 9;44(7):707-721. Epub 2018 May 9.

Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.

Aims: This study aimed to assess clinicopathologic features of transactive response DNA-binding protein of 43 kDa (TDP-43) pathology and its risk factors in multiple system atrophy (MSA).

Methods: Paraffin-embedded sections of the amygdala and basal forebrain from 186 autopsy-confirmed MSA cases were screened with immunohistochemistry for phospho-TDP-43. In cases having TDP-43 pathology, additional brain regions were assessed. Read More

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http://dx.doi.org/10.1111/nan.12485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191374PMC
December 2018
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Expression profile of pattern recognition receptors in skeletal muscle of SOD1 amyotrophic lateral sclerosis (ALS) mice and sporadic ALS patients.

Neuropathol Appl Neurobiol 2018 10 16;44(6):606-627. Epub 2018 Apr 16.

Institute of Neuroanatomy, Medical Clinic RWTH Aachen University, Aachen, Germany.

Aims: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons and progressive muscle wasting. Inflammatory processes, mediated by non-neuronal cells, such as glial cells, are known to contribute to disease progression. Inflammasomes consist of pattern recognition receptors (PRRs), apoptosis-associated speck-like protein (ASC) and caspase 1 and are essential for interleukin (IL) processing and a rapid immune response after tissue damage. Read More

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http://dx.doi.org/10.1111/nan.12483DOI Listing
October 2018
7 Reads