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Neuropathology and Applied Neurobiology

Alan King Lun Liu, Ernest Junwei Lim, Idil Ahmed, Raymond Chuen-Chung Chang, Ronald K B Pearce, Steve M Gentleman
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 (nbM), it has not generally been a focus for studies of neurodegenerative disorders. However, the nvlDBB does have 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...
July 13, 2018: Neuropathology and Applied Neurobiology
A P Kiely, S Miners, R Courtney, C Strand, S Love, J L Holton
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...
July 11, 2018: Neuropathology and Applied Neurobiology
Benjamin Gille, Maxim De Schaepdryver, Janne Goossens, Lieselot Dedeene, Joke De Vocht, Emanuela Oldoni, An Goris, Ludo Van Den Bosch, Bart Depreitere, Kristl G Claeys, Jos Tournoy, Philip Van Damme, Koen Poesen
AIMS: Amyotrophic Lateral Sclerosis (ALS) is the most common motor neuron degeneration disease with a diagnostic delay of about one 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...
June 16, 2018: Neuropathology and Applied Neurobiology
T Zrzavy, R Höftberger, T Berger, H Rauschka, O Butovsky, H Weiner, H Lassmann
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. METHODS: We used recently described markers to characterize the origin and functional states of microglia/macrophages in white and grey matter in patients who died under septic conditions and compared it to those patients without systemic inflammation...
May 27, 2018: Neuropathology and Applied Neurobiology
G Y López, A Perry, B Harding, M Li, M Santi
No abstract text is available yet for this article.
May 27, 2018: Neuropathology and Applied Neurobiology
Y Y Fathy, A J Jonker, E Oudejans, F J J de Jong, A-M W van Dam, A J M Rozemuller, W D J van de Berg
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. METHODS: We analysed postmortem insular tissue from 24 donors with incidental Lewy body disease, PD, PD with dementia (PDD), DLB and age-matched controls...
May 24, 2018: Neuropathology and Applied Neurobiology
H D C Bain, Y S Davidson, A C Robinson, S Ryan, S Rollinson, A Richardson, M Jones, J S Snowden, S Pickering-Brown, D M A Mann
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)...
May 23, 2018: Neuropathology and Applied Neurobiology
S Soponkanaporn, C T Deakin, P W Schutz, L R Marshall, S A Yasin, C M Johnson, E Sag, S L Tansley, N J McHugh, L R Wedderburn, T S Jacques
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 6.3, interquartile range 0.5-15.9) enrolled in the Juvenile Dermatomyositis Cohort and Biomarker Study (JDCBS)...
May 16, 2018: Neuropathology and Applied Neurobiology
Lauri Heiskanen, Katri Kivinen, Maria Gardberg, Pia Wahlsten, Valtteri Kaasinen
No abstract text is available yet for this article.
May 12, 2018: Neuropathology and Applied Neurobiology
J Liu, H Heinsen, L T Grinberg, E Alho, E Amaro, C A Pasqualucci, U Rüb, K Seidel, W den Dunnen, T Arzberger, C Schmitz, M C Kiessling, B Bader, A Danek
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...
May 2, 2018: Neuropathology and Applied Neurobiology
F Marguet, N Piton, H Adle-Biassette, F Renaud, E Bohers, T Boyer, A Zarea, S Derrey, J C Sabourin, A Laquerrière
No abstract text is available yet for this article.
April 21, 2018: Neuropathology and Applied Neurobiology
K-C Wu, H-H Liou, C-Y Lee, C-J Lin
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...
April 21, 2018: Neuropathology and Applied Neurobiology
Sarah Grasedieck, Medhanie Mulaw, Nadine Sperb, Katja Wessinger, Arefeh Rouhi, Martin Bommer, Jacoline E C Bromberg, Markus Otto, Hayrettin Tumani, Christine A F von Arnim, Daniel Mertens, Florian Kuchenbauer
No abstract text is available yet for this article.
April 21, 2018: Neuropathology and Applied Neurobiology
D T Ohm, G Kim, T Gefen, A Rademaker, S Weintraub, E H Bigio, M-M Mesulam, E Rogalski, C Geula
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...
April 21, 2018: Neuropathology and Applied Neurobiology
D Panja, C A Vedeler, M Schubert
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 D28k 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...
April 21, 2018: Neuropathology and Applied Neurobiology
K Yu, A S Youshani, F L Wilkinson, C O'Leary, P Cook, L Laaniste, A Liao, D Mosses, C Waugh, H Shorrock, O Pathmanaban, A Macdonald, I Kamaly-Asl, F Roncaroli, B W Bigger
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...
April 20, 2018: Neuropathology and Applied Neurobiology
J A Cotter, A R Judkins
Meaningful classification of paediatric brain tumours has been a topic of revived discussion in the current era of molecular analysis. In recent years, we have seen the practice of diagnostic neuropathology not only incorporate routine biomarker interpretation (e.g. INI1/SMARCB1 and BRAF V600E immunohistochemistry), but also extend its reach into the molecular pathology laboratory. Next-generation sequencing, fusion analysis, and copy number profiling are now commonly-employed diagnostic tools, particularly in histologically challenging or clinically difficult cases...
April 20, 2018: Neuropathology and Applied Neurobiology
C Ruffmann, N Bengoa-Vergniory, I Poggiolini, D Ritchie, M T Hu, J Alegre-Abarrategui, L Parkkinen
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...
April 19, 2018: Neuropathology and Applied Neurobiology
P J Cimino, R A Yoda, H-G Wirsching, J I Warrick, M O Dorschner, M Ferreira
No abstract text is available yet for this article.
April 19, 2018: Neuropathology and Applied Neurobiology
J J Pruzin, P T Nelson, E L Abner, Z Arvanitakis
Type 2 diabetes (T2D) and Alzheimer's disease (AD) are both highly prevalent diseases worldwide, and each is associated with high-morbidity and high-mortality. Numerous clinical studies have consistently shown that T2D confers a two-fold increased risk for a dementia, including dementia attributable to AD. Yet, the mechanisms underlying this relationship, especially nonvascular mechanisms, remain debated. Cerebral vascular disease (CVD) is likely to be playing a role. But increased AD neuropathologic changes (ADNC), specifically neuritic amyloid plaques (AP) and neurofibrillary tangles (NFT), are also posited mechanisms...
June 2018: Neuropathology and Applied Neurobiology
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