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Acta Neuropathologica Communications

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https://read.qxmd.com/read/30755281/young-adult-onset-very-slowly-progressive-cognitive-decline-with-spastic-paraparesis-in-alzheimer-s-disease-with-cotton-wool-plaques-due-to-a-novel-presenilin1-g417s-mutation
#1
LETTER
Tomoko Miki, Osamu Yokota, Takashi Haraguchi, Takeshi Ikeuchi, Bin Zhu, Shintaro Takenoshita, Seishi Terada, Norihito Yamada
No abstract text is available yet for this article.
February 12, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30755280/heterogeneous-nuclear-ribonucleoproteins-r-and-q-accumulate-in-pathological-inclusions-in-ftld-fus
#2
Lauren M Gittings, Sandrine C Foti, Bridget C Benson, Priya Gami-Patel, Adrian M Isaacs, Tammaryn Lashley
Frontotemporal lobar degeneration (FTLD) is pathologically subdivided based on the presence of particular pathological proteins that are identified in inclusion bodies observed post-mortem. The FTLD-FUS subgroup is defined by the presence of the fused in sarcoma protein (FUS) in pathological inclusions. FUS is a heterogeneous nuclear ribonucleoprotein (hnRNP) protein and a member of the FET (FUS, EWS, TAF15) protein family. It shuttles between the nucleus and cytoplasm, and has been implicated in many cellular functions including translation, splicing, and RNA transport...
February 12, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30744693/endothelial-edema-precedes-blood-brain-barrier-breakdown-in-early-time-points-after-experimental-focal-cerebral-ischemia
#3
Martin Krueger, Bianca Mages, Constance Hobusch, Dominik Michalski
In the setting of stroke, ischemia-related blood-brain barrier (BBB) dysfunction aggravates the cerebral edema, which critically impacts on the clinical outcome. Further, an impaired vascular integrity is associated with the risk of intracranial bleeding, especially after therapeutic recanalization. Therefore, the present study was aimed to investigate early vascular alterations from 30 min to 4 h after experimental middle cerebral artery occlusion (MCAO) in mice. Here, an extravasation of the permeability marker FITC-albumin was detectable in animals 2 and 4 h after MCAO...
February 11, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30732655/white-matter-capillaries-in-vascular-and-neurodegenerative-dementias
#4
Yoshiki Hase, Ren Ding, Gina Harrison, Emily Hawthorne, Amilia King, Sean Gettings, Charlotte Platten, William Stevenson, Lucinda J L Craggs, Raj N Kalaria
Previous studies suggest white matter (WM) integrity is vulnerable to chronic hypoperfusion during brain ageing. We assessed ~ 0.7 million capillary profiles in the frontal lobe WM across several dementias comprising Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease with dementia, vascular dementia, mixed dementias, post-stroke dementia as well as post-stroke no dementia and similar age ageing and young controls without significant brain pathology. Standard histopathological methods were used to determine microvascular pathology and capillary width and densities in 153 subjects using markers of the basement membrane (collagen IV; COL4) and endothelium (glucose transporter-1; GLUT-1)...
February 7, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30722785/ephb2-dependent-signaling-promotes-neuronal-excitotoxicity-and-inflammation-in-the-acute-phase-of-ischemic-stroke
#5
Anne-Sophie Ernst, Laura-Inés Böhler, Anna M Hagenston, Angelika Hoffmann, Sabine Heiland, Carsten Sticht, Martin Bendszus, Markus Hecker, Hilmar Bading, Hugo H Marti, Thomas Korff, Reiner Kunze
Local cerebral hypoperfusion causes ischemic stroke while driving multiple cell-specific responses including inflammation, glutamate-induced neurotoxicity mediated via NMDAR, edema formation and angiogenesis. Despite the relevance of these pathophysiological mechanisms for disease progression and outcome, molecular determinants controlling the onset of these processes are only partially understood. In this context, our study intended to investigate the functional role of EphB2, a receptor tyrosine kinase that is crucial for synapse function and binds to membrane-associated ephrin-B ligands...
February 5, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30704526/microglia-pre-activation-and-neurodegeneration-precipitate-neuroinflammation-without-exacerbating-tissue-injury-in-experimental-autoimmune-encephalomyelitis
#6
Isabella Wimmer, Cornelia Scharler, Tobias Zrzavy, Taro Kadowaki, Verena Mödlagl, Kim Rojc, Anna R Tröscher, Maja Kitic, Shuichi Ueda, Monika Bradl, Hans Lassmann
Human inflammatory or neurodegenerative diseases, such as progressive multiple sclerosis (MS), occur on a background of age-related microglia activation and iron accumulation as well as pre-existing neurodegeneration. Most experimental models for CNS diseases, however, are induced in rodents, which are naturally characterized by a homeostatic microglia phenotype, low cellular iron load and absence of neurodegeneration. Here, we show that naïve LEWzizi rats - Lewis rats with a zitter rat background - show a spontaneous phenotype partly mimicking the changes seen in human aging and particularly in the normal-appearing white and grey matter of patients with progressive MS...
January 31, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30704515/the-apmap-interactome-reveals-new-modulators-of-app-processing-and-beta-amyloid-production-that-are-altered-in-alzheimer-s-disease
#7
Hermeto Gerber, Sebastien Mosser, Benjamin Boury-Jamot, Michael Stumpe, Alessandra Piersigilli, Christine Goepfert, Joern Dengjel, Urs Albrecht, Fulvio Magara, Patrick C Fraering
The adipocyte plasma membrane-associated protein APMAP is expressed in the brain where it associates with γ-secretase, a protease responsible for the generation of the amyloid-β peptides (Aβ) implicated in the pathogenesis of Alzheimer's disease (AD). In this study, behavioral investigations revealed spatial learning and memory deficiencies in our newly generated mouse line lacking the protein APMAP. In a mouse model of AD, the constitutive deletion of APMAP worsened the spatial memory phenotype and led to increased Aβ production and deposition into senile plaques...
January 31, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30691533/apolipoprotein-e-and-clusterin-inhibit-the-early-phase-of-amyloid-%C3%AE-aggregation-in-an-in-vitro-model-of-cerebral-amyloid-angiopathy
#8
Yoshinori Endo, Kazuhiro Hasegawa, Ryo Nomura, Hidetaka Arishima, Ken-Ichiro Kikuta, Taro Yamashita, Yasuteru Inoue, Mitsuharu Ueda, Yukio Ando, Mark R Wilson, Tadanori Hamano, Yasunari Nakamoto, Hironobu Naiki
Sporadic cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid-β (Aβ) deposition, which leads to lobar hemorrhage and dementia. Biological molecules affecting the development of CAA have not been fully characterized. In this study, we performed proteome analysis of biopsied leptomeningeal and cortical vessels obtained from 6 CAA patients and 5 non-CAA patients who underwent surgery for large lobar hemorrhages. We found that 6 proteins, including Aβ, apolipoprotein E (apoE), clusterin (CLU), albumin, complement C4 and vitronectin were significantly upregulated in the vessels of CAA patients as compared to non-CAA patients...
January 28, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30678721/absence-of-endothelial-%C3%AE-5%C3%AE-1-integrin-triggers-early-onset-of-experimental-autoimmune-encephalomyelitis-due-to-reduced-vascular-remodeling-and-compromised-vascular-integrity
#9
Ravi Kant, Sebok K Halder, Gregory J Bix, Richard Milner
Early in the development of multiple sclerosis (MS) and its mouse model experimental autoimmune encephalomyelitis (EAE), vascular integrity is compromised. This is accompanied by a marked vascular remodeling response, though it is currently unclear whether this is an adaptive vascular repair mechanism or is part of the pathogenic process. In light of the well-described angiogenic role for the α5β1 integrin, the goal of this study was to evaluate how genetic deletion of endothelial α5 integrin (α5-EC-KO mice) impacts vascular remodeling and repair following vascular disruption during EAE pathogenesis, and how this subsequently influences clinical progression and inflammatory demyelination...
January 24, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30674342/enhanced-phosphorylation-of-t153-in-soluble-tau-is-a-defining-biochemical-feature-of-the-a152t-tau-risk-variant
#10
Yari Carlomagno, Dah-Eun Chloe Chung, Mei Yue, Aishe Kurti, Nicole M Avendano, Monica Castanedes-Casey, Kelly M Hinkle, Karen Jansen-West, Lillian M Daughrity, Jimei Tong, Virginia Phillips, Rosa Rademakers, Michael DeTure, John D Fryer, Dennis W Dickson, Leonard Petrucelli, Casey Cook
Pathogenic mutations in the tau gene (microtubule associated protein tau, MAPT) are linked to the onset of tauopathy, but the A152T variant is unique in acting as a risk factor for a range of disorders including Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and dementia with Lewy bodies (DLB). In order to provide insight into the mechanism by which A152T modulates disease risk, we developed a novel mouse model utilizing somatic brain transgenesis with adeno-associated virus (AAV) to drive tau expression in vivo, and validated the model by confirming the distinct biochemical features of A152T tau in postmortem brain tissue from human carriers...
January 23, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30657060/preventive-action-of-benztropine-on-platinum-induced-peripheral-neuropathies-and-tumor-growth
#11
Olivier Cerles, Tânia Cristina Gonçalves, Sandrine Chouzenoux, Evelyne Benoit, Alain Schmitt, Nathaniel Edward Bennett Saidu, Niloufar Kavian, Christiane Chéreau, Camille Gobeaux, Bernard Weill, Romain Coriat, Carole Nicco, Frédéric Batteux
The endogenous cholinergic system plays a key role in neuronal cells, by suppressing neurite outgrowth and myelination and, in some cancer cells, favoring tumor growth. Platinum compounds are widely used as part of first line conventional cancer chemotherapy; their efficacy is however limited by peripheral neuropathy as a major side-effect. In a multiple sclerosis mouse model, benztropine, that also acts as an anti-histamine and a dopamine re-uptake inhibitor, induced the differentiation of oligodendrocytes through M1 and M3 muscarinic receptors and enhanced re-myelination...
January 18, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30646956/regulation-of-dopamine-neurotransmission-from-serotonergic-neurons-by-ectopic-expression-of-the-dopamine-d2-autoreceptor-blocks-levodopa-induced-dyskinesia
#12
Rhyomi C Sellnow, Jordan H Newman, Nicole Chambers, Anthony R West, Kathy Steece-Collier, Ivette M Sandoval, Matthew J Benskey, Christopher Bishop, Fredric P Manfredsson
Levodopa-induced dyskinesias (LID) are a prevalent side effect of chronic treatment with levodopa (L-DOPA) for the motor symptoms of Parkinson's disease (PD). It has long been hypothesized that serotonergic neurons of the dorsal raphe nucleus (DRN) are capable of L-DOPA uptake and dysregulated release of dopamine (DA), and that this "false neurotransmission" phenomenon is a main contributor to LID development. Indeed, many preclinical studies have demonstrated LID management with serotonin receptor agonist treatment, but unfortunately, promising preclinical data has not been translated in large-scale clinical trials...
January 15, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30642400/als-linked-fus-mutations-confer-loss-and-gain-of-function-in-the-nucleus-by-promoting-excessive-formation-of-dysfunctional-paraspeckles
#13
Haiyan An, Lucy Skelt, Antonietta Notaro, J Robin Highley, Archa H Fox, Vincenzo La Bella, Vladimir L Buchman, Tatyana A Shelkovnikova
Mutations in the FUS gene cause amyotrophic lateral sclerosis (ALS-FUS). Mutant FUS is known to confer cytoplasmic gain of function but its effects in the nucleus are less understood. FUS is an essential component of paraspeckles, subnuclear bodies assembled on a lncRNA NEAT1. Paraspeckles may play a protective role specifically in degenerating spinal motor neurons. However it is still unknown how endogenous levels of mutant FUS would affect NEAT1/paraspeckles. Using novel cell lines with the FUS gene modified by CRISPR/Cas9 and human patient fibroblasts, we found that endogenous levels of mutant FUS cause accumulation of NEAT1 isoforms and paraspeckles...
January 14, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30626447/low-level-blast-exposure-disrupts-gliovascular-and-neurovascular-connections-and-induces-a-chronic-vascular-pathology-in-rat-brain
#14
Miguel A Gama Sosa, Rita De Gasperi, Georgina S Perez Garcia, Gissel M Perez, Courtney Searcy, Danielle Vargas, Alicia Spencer, Pierce L Janssen, Anna E Tschiffely, Richard M McCarron, Benjamin Ache, Rajaram Manoharan, William G Janssen, Susan J Tappan, Russell W Hanson, Sam Gandy, Patrick R Hof, Stephen T Ahlers, Gregory A Elder
Much concern exists over the role of blast-induced traumatic brain injury (TBI) in the chronic cognitive and mental health problems that develop in veterans and active duty military personnel. The brain vasculature is particularly sensitive to blast injury. The aim of this study was to characterize the evolving molecular and histologic alterations in the neurovascular unit induced by three repetitive low-energy blast exposures (3 × 74.5 kPa) in a rat model mimicking human mild TBI or subclinical blast exposure...
January 9, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30626432/increased-plasma-neurofilament-light-chain-concentration-correlates-with-severity-of-post-mortem-neurofibrillary-tangle-pathology-and-neurodegeneration
#15
Nicholas J Ashton, Antoine Leuzy, Yau Mun Lim, Claire Troakes, Tibor Hortobágyi, Kina Höglund, Dag Aarsland, Simon Lovestone, Michael Schöll, Kaj Blennow, Henrik Zetterberg, Abdul Hye
Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tangles and widespread neuronal loss in the brain. In recent years, blood biomarkers have emerged as a realistic prospect to highlight accumulating pathology for secondary prevention trials. Neurofilament light chain (NfL), a marker of axonal degeneration, is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. A strong relationship with cerebrospinal fluid (CSF) NfL suggests that these biomarker modalities reflect the same pathological process...
January 9, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30616676/optic-nerve-thinning-and-neurosensory-retinal-degeneration-in-the-rtg4510-mouse-model-of-frontotemporal-dementia
#16
Ian F Harrison, Rozalind Whitaker, Pietro Maria Bertelli, James M O'Callaghan, Lajos Csincsik, Martina Bocchetta, Da Ma, Alice Fisher, Zeshan Ahmed, Tracey K Murray, Michael J O'Neill, Jonathan D Rohrer, Mark F Lythgoe, Imre Lengyel
Visual impairments, such as difficulties in reading and finding objects, perceiving depth and structure from motion, and impaired stereopsis, have been reported in tauopathy disorders, such as frontotemporal dementia (FTD). These impairments however have been previously attributed to cortical pathologies rather than changes in the neurosensory retina or the optic nerve. Here, we examined tau pathology in the neurosensory retina of the rTg(tauP301L)4510 mouse model of FTD. Optic nerve pathology in mice was also assessed using MRI, and corresponding measurements taken in a cohort of five FTD sufferers and five healthy controls...
January 7, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30611313/-dusty-core-disease-ducd-expanding-morphological-spectrum-of-ryr1-recessive-myopathies
#17
Matteo Garibaldi, John Rendu, Julie Brocard, Emmanuelle Lacene, Julien Fauré, Guy Brochier, Maud Beuvin, Clemence Labasse, Angeline Madelaine, Edoardo Malfatti, Jorge Alfredo Bevilacqua, Fabiana Lubieniecki, Soledad Monges, Ana Lia Taratuto, Jocelyn Laporte, Isabelle Marty, Giovanni Antonini, Norma Beatriz Romero
Several morphological phenotypes have been associated to RYR1-recessive myopathies. We recharacterized the RYR1-recessive morphological spectrum by a large monocentric study performed on 54 muscle biopsies from a large cohort of 48 genetically confirmed patients, using histoenzymology, immunohistochemistry, and ultrastructural studies. We also analysed the level of RyR1 expression in patients' muscle biopsies. We defined "dusty cores" the irregular areas of myofibrillar disorganisation characterised by a reddish-purple granular material deposition with uneven oxidative stain and devoid of ATPase activity, which represent the characteristic lesion in muscle biopsy in 54% of patients...
January 5, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30606258/a-pathogenic-tau-fragment-compromises-microtubules-disrupts-insulin-signaling-and-induces-the-unfolded-protein-response
#18
Tong Guo, Dina Dakkak, Teresa Rodriguez-Martin, Wendy Noble, Diane P Hanger
Human tauopathies including Alzheimer's disease, progressive supranuclear palsy and related disorders, are characterized by deposition of pathological forms of tau, synaptic dysfunction and neuronal loss. We have previously identified a pathogenic C-terminal tau fragment (Tau35) that is associated with human tauopathy. However, it is not known how tau fragmentation affects critical molecular processes in cells and contributes to impaired physiological function. Chinese hamster ovary (CHO) cells and new CHO cell lines stably expressing Tau35 or full-length human tau were used to compare the effects of disease-associated tau cleavage on tau function and signaling pathways...
January 3, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30606247/clinical-and-neuropathological-phenotype-associated-with-the-novel-v189i-mutation-in-the-prion-protein-gene
#19
Giuseppe Di Fede, Marcella Catania, Cristiana Atzori, Fabio Moda, Claudio Pasquali, Antonio Indaco, Marina Grisoli, Marta Zuffi, Maria Cristina Guaita, Roberto Testi, Stefano Taraglio, Maria Sessa, Graziano Gusmaroli, Mariacarmela Spinelli, Giulia Salzano, Giuseppe Legname, Roberto Tarletti, Laura Godi, Maurizio Pocchiari, Fabrizio Tagliavini, Daniele Imperiale, Giorgio Giaccone
Prion diseases are neurodegenerative disorders which are caused by an accumulation of the abnormal, misfolded prion protein known as scrapie prion protein (PrPSc ). These disorders are unique as they occur as sporadic, genetic and acquired forms. Sporadic Creutzfeldt-Jakob Disease (CJD) is the most common human prion disease, accounting for approximately 85-90% of cases, whereas autosomal dominant genetic forms, due to mutations in the prion protein gene (PRNP), account for 10-15% of cases. Genetic forms show a striking variability in their clinical and neuropathological picture and can sometimes mimic other neurodegenerative diseases...
January 3, 2019: Acta Neuropathologica Communications
https://read.qxmd.com/read/30593285/amyloid-beta-and-phosphorylated-tau-in-post-mortem-alzheimer-s-disease-retinas
#20
Jurre den Haan, Tjado H J Morrema, Frank D Verbraak, Johannes F de Boer, Philip Scheltens, Annemieke J Rozemuller, Arthur A B Bergen, Femke H Bouwman, Jeroen J Hoozemans
In-vivo labeling of retinal amyloid-beta(Aβ) and tau has potential as non-invasive biomarker for Alzheimer's disease (AD). However, literature on the presence of Aβ and phosphorylated tau (pTau) in AD retinas is inconclusive. We therefore assessed the presence of Aβ and pTau in post-mortem retinas in 6 AD and 6 control cases who donated brains and eyes to the Netherlands Brain Bank. Neuropathological diagnosis of AD was made according to NIA-AA criteria. Formalin fixed retinas were dissected in quadrants and cross-sections of medial and superior retinas were made...
December 28, 2018: Acta Neuropathologica Communications
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