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https://www.readbyqxmd.com/read/28844104/co-administration-of-tio2-nanowired-mesenchymal-stem-cells-with-cerebrolysin-potentiates-neprilysin-level-and-reduces-brain-pathology-in-alzheimer-s-disease
#1
Hari Shanker Sharma, Dafin Fior Muresanu, José Vicente Lafuente, Ranjana Patnaik, Z Ryan Tian, Asya Ozkizilcik, Rudy J Castellani, Herbert Mössler, Aruna Sharma
Neprilysin (NPL), the rate-limiting enzyme for amyloid beta peptide (AβP), appears to play a crucial role in the pathogenesis of Alzheimer's disease (AD). Since mesenchymal stem cells (MSCs) and/or cerebrolysin (CBL, a combination of neurotrophic factors and active peptide fragments) have neuroprotective effects in various CNS disorders, we examined nanowired delivery of MSCs and CBL on NPL content and brain pathology in AD using a rat model. AD-like symptoms were produced by intraventricular (i.c.v.) administration of AβP (1-40) in the left lateral ventricle (250 ng/10 μl, once daily) for 4 weeks...
August 26, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28766965/map2-ihc-detection-a-marker-of-antigenicity-in-cns-tissues
#2
M R D'Andrea, R J Howanski, C F Saller
Immunohistochemistry (IHC) is used to detect antibody-specific antigens in tissues; the results depend on the ability of the primary antibodies to bind to their antigens. Therefore, results depend on the quality of preservation of the specimen. Many investigators have overcome the deleterious effects of over-fixation on the binding of primary antibodies to specimen antigens using IHC, but if the specimen is under-fixed or fixation is delayed, false negative results could be obtained despite certified laboratory practices...
August 2, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/28750656/oligomeric-amyloid-beta-induces-mapk-mediated-activation-of-brain-cytosolic-and-calcium-independent-phospholipase-a2-in-a-spatial-specific-manner
#3
Juan Pablo Palavicini, Chunyan Wang, Linyuan Chen, Kristen Hosang, Jianing Wang, Takami Tomiyama, Hiroshi Mori, Xianlin Han
Alzheimer's disease (AD) is histopathologically characterized by the build-up of fibrillar amyloid beta (Aβ) in the form of amyloid plaques and the development of intraneuronal neurofibrillary tangles consisting of aggregated hyperphosphorylated Tau. Although amyloid fibrils were originally considered responsible for AD pathogenesis, recent convincing evidence strongly implicates soluble oligomeric Aβ as the primary neurotoxic species driving disease progression. A third largely ignored pathological hallmark, originally described by Alois Alzheimer, is the presence of "adipose inclusions", suggestive of aberrant lipid metabolism...
July 27, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28730955/itraq-based-proteomic-analysis-of-appsw-ind-mice-provides-insights-into-the-early-changes-in-alzheimer-s-disease
#4
Nan Li, Pinghong Hu, Tiantian Xu, Huan Chen, Xiaoying Chen, Jianwen Hu, Xifei Yang, Lei Shi, Jian-Hong Luo, Junyu Xu
BACKGROUND: Several proteins have been identified as potential diagnostic biomarkers in imaging, genetic, or proteomic studies in Alzheimer disease (AD) patients and mouse models. However, biomarkers for presymptom diagnosis of AD are still under investigation, as are the presymptom molecular changes in AD pathogenesis. OBJECTIVE: In this study, we aim to analyzed the early proteomic changes in APPSw,Ind mice and to conduct further functional studies on interesting proteins...
July 19, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28638989/parietal-white-matter-lesions-in-alzheimer-s-disease-are-associated-with-cortical-neurodegenerative-pathology-but-not-with-small-vessel-disease
#5
Kirsty E McAleese, Lauren Walker, Sophie Graham, Elisa L J Moya, Mary Johnson, Daniel Erskine, Sean J Colloby, Madhurima Dey, Carmen Martin-Ruiz, John-Paul Taylor, Alan J Thomas, Ian G McKeith, Charles De Carli, Johannes Attems
Cerebral white matter lesions (WML) encompass axonal loss and demyelination, and the pathogenesis is assumed to be small vessel disease (SVD)-related ischemia. However, WML may also result from the activation of Wallerian degeneration as a consequence of cortical Alzheimer's disease (AD) pathology, i.e. hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ) deposition. WML seen in AD have a posterior predominance compared to non-demented individuals but it is unclear whether the pathological and molecular signatures of WML differ between these two groups...
June 21, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28623948/one-carbon-metabolism-cognitive-impairment-and-csf-measures-of-alzheimer-pathology-homocysteine-and-beyond
#6
Loïc Dayon, Seu Ping Guiraud, John Corthésy, Laeticia Da Silva, Eugenia Migliavacca, Domilė Tautvydaitė, Aikaterini Oikonomidi, Barbara Moullet, Hugues Henry, Sylviane Métairon, Julien Marquis, Patrick Descombes, Sebastiano Collino, François-Pierre J Martin, Ivan Montoliu, Martin Kussmann, Jérôme Wojcik, Gene L Bowman, Julius Popp
BACKGROUND: Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults...
June 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28582448/acid-sphingomyelinase-deficiency-enhances-myelin-repair-after-acute-and-chronic-demyelination
#7
Marwan Chami, Ramona Halmer, Laura Schnoeder, Katrin Anne Becker, Carola Meier, Klaus Fassbender, Erich Gulbins, Silke Walter
The cuprizone animal model, also known as the toxic demyelination model, is a well-reproducible model of demyelination- and remyelination in mice, and has been useful in studying important aspect of human demyelinating diseases, including multiple sclerosis. In this study, we investigated the role of acid sphingomyelinase in demyelination and myelin repair by inducing acute and chronic demyelination with 5- or 12-week cuprizone treatment, followed by a 2-week cuprizone withdrawal phase to allow myelin repair...
2017: PloS One
https://www.readbyqxmd.com/read/28569617/multimodal-partial-volume-correction-application-to-11-c-pib-pet-mri-myelin-imaging-in-multiple-sclerosis
#8
Elisabetta Grecchi, Mattia Veronese, Benedetta Bodini, Daniel García-Lorenzo, Marco Battaglini, Bruno Stankoff, Federico E Turkheimer
The [(11)C]PIB PET tracer, originally developed for amyloid imaging, has been recently repurposed to quantify demyelination and remyelination in multiple sclerosis (MS). Myelin PET imaging, however, is limited by its low resolution that deteriorates the quantification accuracy of white matter (WM) lesions. Here, we introduce a novel partial volume correction (PVC) method called Multiresolution-Multimodal Resolution-Recovery (MM-RR), which uses the wavelet transform and a synergistic statistical model to exploit MRI structural images to improve the resolution of [(11)C]PIB PET myelin imaging...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28547865/re-imagining-alzheimer-s-disease-the-diminishing-importance-of-amyloid-and-a-glimpse-of-what-lies-ahead
#9
REVIEW
Kai-Hei Tse, Karl Herrup
Many have criticized the amyloid cascade hypothesis of Alzheimer's disease for its inconsistencies and failures to either accurately predict disease symptoms or guide the development of productive therapies. In addition to criticisms, however, we believe that the field would benefit from having alternative narratives and disease models that can either replace or function alongside of an amyloid-centric view of Alzheimer's. This review is an attempt to meet that need. We offer three experimentally verified amyloid-independent mechanisms, each of which plausibly contributes substantially to the aetiology of Alzheimer's disease: loss of DNA integrity, faulty cell cycle regulation, regression of myelination...
May 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28535786/biochemical-markers-in-vascular-cognitive-impairment-associated-with-subcortical-small-vessel-disease-a-consensus-report
#10
A Wallin, E Kapaki, M Boban, S Engelborghs, D M Hermann, B Huisa, M Jonsson, M G Kramberger, L Lossi, B Malojcic, S Mehrabian, A Merighi, E B Mukaetova-Ladinska, G P Paraskevas, B O Popescu, R Ravid, L Traykov, G Tsivgoulis, G Weinstein, A Korczyn, M Bjerke, G Rosenberg
BACKGROUND: Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data...
May 23, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28478826/novel-aspects-of-defensins-involvement-in-virus-induced-autoimmunity-in-the-central-nervous-system
#11
Evangelos I Kazakos, Jannis Kountouras, Stergios A Polyzos, Georgia Deretzi
Recent research on re-circulation of interstitial fluid from the brain parenchyma to the periphery and its inferred importance in immune surveillance dysregulation are changing our conceptualization of the pathophysiology of virus-induced autoimmunity. In this context, it is necessary to reassess the immunomodulatory properties of human defensins that are variably expressed by cerebral microglia, astrocytes and choroid plexus epithelial cells and exhibit complex and often confounding roles in neuroinflammatory processes...
May 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28453483/remyelination-a-potential-therapeutic-strategy-for-alzheimer-s-disease
#12
Junjun Sun, Hong Zhou, Feng Bai, Zhijun Zhang, Qingguo Ren
Myelin is a lipid-rich multilamellar membrane that wraps around long segments of neuronal axons and it increases the conduction of action potentials, transports the necessary trophic support to the neuronal axons, and reduces the energy consumed by the neuronal axons. Together with axons, myelin is a prerequisite for the higher functions of the central nervous system and complex forms of network integration. Myelin impairments have been suggested to lead to neuronal dysfunction and cognitive decline. Accumulating evidence, including brain imaging and postmortem and genetic association studies, has implicated myelin impairments in Alzheimer's disease (AD)...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28452087/cytotoxic-cd8-t-cells-ablation-enhances-the-capacity-of-regulatory-t-cells-to-delay-viral-elimination-in-theiler-s-murine-encephalomyelitis
#13
Malgorzata Ciurkiewicz, Vanessa Herder, Muhammad Akram Khan, Ann-Kathrin Uhde, René Teich, Stephan Floess, Wolfgang Baumgärtner, Jochen Huehn, Andreas Beineke
Theiler's murine encephalomyelitis (TME) of susceptible mouse strains is a commonly used infectious animal model for multiple sclerosis. The study aim was to test the hypothesis whether cytotoxic T cell responses account for the limited impact of regulatory T cells on antiviral immunity in TME virus-induced demyelinating disease (TMEV-IDD) resistant C57BL/6 mice. TME virus-infected C57BL/6 mice were treated with (i) interleukin-2/-anti-interleukin-2-antibody-complexes to expand regulatory T cells ('Treg-expansion'), (ii) anti-CD8-antibodies to deplete cytotoxic T cells ('CD8-depletion') or (iii) with a combination of Treg-expansion and CD8-depletion ('combined treatment') prior to infection...
April 27, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28432486/cholesterol-as-a-modifying-agent-of-the-neurovascular-unit-structure-and-function-under-physiological-and-pathological-conditions
#14
REVIEW
Ewelina Czuba, Aleksandra Steliga, Grażyna Lietzau, Przemysław Kowiański
The brain, demanding constant level of cholesterol, precisely controls its synthesis and homeostasis. The brain cholesterol pool is almost completely separated from the rest of the body by the functional blood-brain barrier (BBB). Only a part of cholesterol pool can be exchanged with the blood circulation in the form of the oxysterol metabolites such, as 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC). Not only neurons but also blood vessels and neuroglia, constituting neurovascular unit (NVU), are crucial for the brain cholesterol metabolism and undergo precise regulation by numerous modulators, metabolites and signal molecules...
August 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28413924/erythropoietin-attenuates-axonal-injury-after-middle-cerebral-artery-occlusion-in-mice
#15
Rongliang Wang, Haiping Zhao, Jincheng Li, Yunxia Duan, Zhibin Fan, Zhen Tao, Fei Ju, Feng Yan, Yumin Luo
OBJECTIVE: Erythropoietin (EPO) confers potent neuroprotection against ischemic injury through a variety of mechanisms. However, the protective effect of EPO on axons after cerebral ischemia in adult mice is rarely covered. The purpose of this study was to investigate the potential neuroprotective effects of EPO on axons in mice after cerebral ischemia. METHODS: A total of 30 adult male C57 BL/6 mice were treated with EPO (5000 IU/kg) or vehicle after transient middle cerebral artery occlusion (MCAO)...
June 2017: Neurological Research
https://www.readbyqxmd.com/read/28334857/co-cultures-with-stem-cell-derived-human-sensory-neurons-reveal-regulators-of-peripheral-myelination
#16
Alex J Clark, Malte S Kaller, Jorge Galino, Hugh J Willison, Simon Rinaldi, David L H Bennett
See Saporta and Shy (doi:10.1093/awx048) for a scientific commentary on this article.Effective bidirectional signalling between axons and Schwann cells is essential for both the development and maintenance of peripheral nerve function. We have established conditions by which human induced pluripotent stem cell-derived sensory neurons can be cultured with rat Schwann cells, and have produced for the first time long-term and stable myelinating co-cultures with human neurons. These cultures contain the specialized domains formed by axonal interaction with myelinating Schwann cells, such as clustered voltage-gated sodium channels at the node of Ranvier and Shaker-type potassium channel (Kv1...
April 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28291839/microstructural-white-matter-alterations-in-preclinical-alzheimer-s-disease-detected-using-free-water-elimination-diffusion-tensor-imaging
#17
Andrew R Hoy, Martina Ly, Cynthia M Carlsson, Ozioma C Okonkwo, Henrik Zetterberg, Kaj Blennow, Mark A Sager, Sanjay Asthana, Sterling C Johnson, Andrew L Alexander, Barbara B Bendlin
Brain changes associated with Alzheimer's disease (AD) begin decades before disease diagnosis. While β-amyloid plaques and neurofibrillary tangles are defining features of AD, neuronal loss and synaptic pathology are closely related to the cognitive dysfunction. Brain imaging methods that are tuned to assess degeneration of myelinated nerve fibers in the brain (collectively called white matter) include diffusion tensor imaging (DTI) and related techniques, and are expected to shed light on disease-related loss of structural connectivity...
2017: PloS One
https://www.readbyqxmd.com/read/28282924/autophagy-and-microglia-novel-partners-in-neurodegeneration-and-aging
#18
REVIEW
Ainhoa Plaza-Zabala, Virginia Sierra-Torre, Amanda Sierra
Autophagy is emerging as a core regulator of Central Nervous System (CNS) aging and neurodegeneration. In the brain, it has mostly been studied in neurons, where the delivery of toxic molecules and organelles to the lysosome by autophagy is crucial for neuronal health and survival. However, we propose that the (dys)regulation of autophagy in microglia also affects innate immune functions such as phagocytosis and inflammation, which in turn contribute to the pathophysiology of aging and neurodegenerative diseases...
March 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28269776/amyloid-related-imaging-abnormalities-in%C3%A2-an-aged-squirrel-monkey-with-cerebral-amyloid-angiopathy
#19
Eric Heuer, Jessica Jacobs, Rebecca Du, Silun Wang, Orion P Keifer, Amarallys F Cintron, Jeromy Dooyema, Yuguang Meng, Xiaodong Zhang, Lary C Walker
Amyloid-related imaging abnormalities (ARIA) in magnetic resonance imaging scans have emerged as indicators of potentially serious side effects in clinical trials of therapeutics for Alzheimer's disease. These anomalies include an edematous type (ARIA-E) that appears as hyperintense (bright) regions by T2-weighted MRI, and a type characterized by the deposition of hemosiderin (ARIA-H) that elicits a hypointense signal, especially in T2* susceptibility weighted images. ARIA in general has been linked to the presence of amyloid-β (Aβ)-type cerebral amyloid angiopathy, an accumulation of misfolded Aβ protein in the vascular wall that impairs the integrity of brain blood vessels...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28220655/ppars-in-the-central-nervous-system-roles-in-neurodegeneration-and-neuroinflammation
#20
Juan M Zolezzi, Manuel J Santos, Sussy Bastías-Candia, Claudio Pinto, Juan A Godoy, Nibaldo C Inestrosa
Over 25 years have passed since peroxisome proliferators-activated receptors (PPARs), were first described. Like other members of the nuclear receptors superfamily, PPARs have been defined as critical sensors and master regulators of cellular metabolism. Recognized as ligand-activated transcription factors, they are involved in lipid, glucose and amino acid metabolism, taking part in different cellular processes, including cellular differentiation and apoptosis, inflammatory modulation and attenuation of acute and chronic neurological damage in vivo and in vitro...
February 20, 2017: Biological Reviews of the Cambridge Philosophical Society
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