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https://www.readbyqxmd.com/read/29146478/diacylglycerols-as-biomarkers-of-sustained-immune-activation-in-proteinopathies-associated-with-dementia
#1
REVIEW
Paul L Wood, John E Cebak, Randall L Woltjer
Cognitive decline is a devastating clinical condition, heavily correlated with age progression. In the cases of Alzheimer's disease, Parkinson's disease, and Lewy body disease, the common neuropathologies are proteinopathies and neuroinflammation. Herein, we review current lipidomics findings and conclude that brain and circulating diacylglycerols represent biomarkers of this ongoing sustained immune response, presumably involving microglia. We further hypothesize that a logical next step will be to evaluate biomarkers of immune activation in a cohort of patients with Mild Cognitive Impairment (MCI) and subsequently attempt to provide therapeutic intervention with anti-inflammatory therapy in MCI patients with immune activation...
November 13, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29142315/hiv-1-counteracts-an-innate-restriction-by-amyloid-precursor-protein-resulting-in-neurodegeneration
#2
Qingqing Chai, Vladimir Jovasevic, Viacheslav Malikov, Yosef Sabo, Scott Morham, Derek Walsh, Mojgan H Naghavi
While beta-amyloid (Aβ), a classic hallmark of Alzheimer's disease (AD) and dementia, has long been known to be elevated in the human immunodeficiency virus type 1 (HIV-1)-infected brain, why and how Aβ is produced, along with its contribution to HIV-associated neurocognitive disorder (HAND) remains ill-defined. Here, we reveal that the membrane-associated amyloid precursor protein (APP) is highly expressed in macrophages and microglia, and acts as an innate restriction against HIV-1. APP binds the HIV-1 Gag polyprotein, retains it in lipid rafts and blocks HIV-1 virion production and spread...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142138/chitotriosidase-chit1-is-increased-in-microglia-and-macrophages-in-spinal-cord-of-amyotrophic-lateral-sclerosis-and-cerebrospinal-fluid-levels-correlate-with-disease-severity-and-progression
#3
Petra Steinacker, Federico Verde, Lubin Fang, Emily Feneberg, Patrick Oeckl, Sigrun Roeber, Sarah Anderl-Straub, Adrian Danek, Janine Diehl-Schmid, Klaus Fassbender, Klaus Fliessbach, Hans Foerstl, Armin Giese, Holger Jahn, Jan Kassubek, Johannes Kornhuber, G Bernhard Landwehrmeyer, Martin Lauer, Elmar Hans Pinkhardt, Johannes Prudlo, Angela Rosenbohm, Anja Schneider, Matthias L Schroeter, Hayrettin Tumani, Christine A F von Arnim, Jochen Weishaupt, Patrick Weydt, Albert C Ludolph, Deniz Yilmazer Hanke, Markus Otto
OBJECTIVES: Neurochemical markers of amyotrophic lateral sclerosis (ALS) that reflect underlying disease mechanisms might help in diagnosis, staging and prediction of outcome. We aimed at determining the origin and differential diagnostic and prognostic potential of the putative marker of microglial activation chitotriosidase (CHIT1). METHODS: Altogether 316 patients were included, comprising patients with sporadic ALS, ALS mimics (disease controls (DCo)), frontotemporal lobar degeneration (FTLD), Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), Parkinson's disease (PD) and healthy controls (Con)...
November 15, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29139169/sex-differences-in-the-phagocytic-and-migratory-activity-of-microglia-and-their-impairment-by-palmitic-acid
#4
Natalia Yanguas-Casás, Andrea Crespo-Castrillo, Maria L de Ceballos, Julie A Chowen, Iñigo Azcoitia, Maria Angeles Arevalo, Luis M Garcia-Segura
Sex differences in the incidence, clinical manifestation, disease course, and prognosis of neurological diseases, such as autism spectrum disorders or Alzheimer's disease, have been reported. Obesity has been postulated as a risk factor for cognitive decline and Alzheimer's disease and, during pregnancy, increases the risk of autism spectrum disorders in the offspring. Obesity is associated with increased serum and brain levels of free fatty acids, such as palmitic acid, which activate microglial cells triggering a potent inflammatory cascade...
November 15, 2017: Glia
https://www.readbyqxmd.com/read/29137922/extracellular-vesicles-in-neurodegenerative-diseases
#5
REVIEW
Tommaso Croese, Roberto Furlan
Extracellular vesicles (EVs) are released by all neural cells, including neurons, oligodendrocytes, astrocytes, and microglia. The lack of adequate technology has not halted neuroscientists from investigating EVs as a mean to decipher neurodegenerative disorders, still in search of comprehensible pathogenic mechanisms and efficient treatment. EVs are thought to be one of ways neurodegenerative pathologies spread in the brain, but also one of the ways the brain tries to displace toxic proteins, making their meaning in pathogenesis uncertain...
November 11, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29127006/srage-prolonged-stem-cell-survival-and-suppressed-rage-related-inflammatory-cell-and-t-lymphocyte-accumulations-in-an-alzheimer-s-disease-model
#6
Seyeon Oh, Myeongjoo Son, Junwon Choi, Sojung Lee, Kyunghee Byun
The main causes of Alzheimer's disease (AD) have not determined despite extensive researches and many clinical trials, and as yet, no effective treatment has been developed. Fortunately, stem cell transplantation is emerging as potential therapeutic candidate for AD, but the success of stem cell based therapy depends on the survival of transplanted cells. Here, we generated sRAGE secreting mesenchymal stem cells (sRAGE-MSCs) and then injected theses MSCs or control MSCs with amyloid beta 1-42 (Aβ1-42) into the entorhinal cortices of male Sprague Dawley rats...
November 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29126976/involvement-of-glucose-related-energy-crisis-and-endoplasmic-reticulum-stress-insinuation-of-streptozotocin-induced-alzheimer-s-like-pathology
#7
Joyshree Biswas, Sonam Gupta, Dinesh Kumar Verma, Parul Gupta, Abhishek Singh, Shubhangini Tiwari, Poonam Goswami, Sharad Sharma, Sarika Singh
The present study was conducted to correlate the cellular and molecular alterations in Alzheimer's pathology employing streptozotocin (STZ) induced experimental rat model. The STZ was administered in rat brain bilaterally by intracerebroventricular route using stereotaxic surgery followed by donepezil dosing. The Alzheimer's related pathological marker like acetylcholinesterase (AChE) activity, tau phosphorylation and amyloid aggregation were observed after STZ administration. STZ treatment showed decreased glucose and glucose transporters (GLUT) level along with augmented level of calcium in both cortical and hippocampal regions of rat brain...
November 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29126887/combined-administration-of-resolvin-e1-and-lipoxin-a4-resolves-inflammation-in-a-murine-model-of-alzheimer-s-disease
#8
Alpdogan Kantarci, Nurgul Aytan, Iro Palaska, Danielle Stephens, Leah Crabtree, Claudia Benincasa, Bruce G Jenkins, Isabel Carreras, Alpaslan Dedeoglu
Dysfunction in the resolution of inflammation may play a key role in Alzheimer's disease (AD). In this study, we found that the levels of specialized pro-resolving lipid mediators (SPMs) in the hippocampus of 5xFAD mice are significantly lower than in non-transgenic littermates. We, therefore, tested the hypothesis that treatment with resolvin E1 (RvE1) and lipoxin A4 (LXA4) alone or in combination will reverse the neuroinflammatory process and decrease Aβ pathology. 5xFAD mice were treated intraperitoneally starting at 1month of age with RvE1 or LXA4 alone or in combination at a dose of 1...
November 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29125117/research-advances-in-the-neuroinflammation-in-alzheimer-s-disease
#9
Wen-Pei Ma, Xuan Zhang, Qiong Wu
Alzheimer's disease(AD) is a chronic degenerative disease of the nervous system,and the pathological change of AD is the formation of senile plaques containing amyloid β(Aβ) and the neurofibrillary tangles. AD patients and animal models exhibit the over activation of microglia(MG) and astrocytes,causing neuroinflammation,leading to neuron death. Inhibition of MG activity can alleviate Aβ plaques. A growing number of studies have found that neuroinflammation is involved in the development and progression of AD...
October 30, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/29122458/adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia-alsp-integrating-the-literature-on-hereditary-diffuse-leukoencephalopathy-with-spheroids-hdls-and-pigmentary-orthochromatic-leukodystrophy-pold
#10
REVIEW
Scott J Adams, Andrew Kirk, Roland N Auer
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a progressive degenerative white matter disorder. ALSP was previously recognized as two distinct entities, hereditary diffuse leukoencephalopathy with spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD). However, recent identification of mutations in the tyrosine kinase domain of the colony stimulating factor 1 receptor (CSF1R) gene, which regulates mononuclear cell lineages including microglia, have provided genetic and mechanistic evidence that POLD and HDLS should be regarded as a single clinicopathologic entity...
November 6, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29106824/inferring-relevant-cell-types-for-complex-traits-by-using-single-cell-gene-expression
#11
Diego Calderon, Anand Bhaskar, David A Knowles, David Golan, Towfique Raj, Audrey Q Fu, Jonathan K Pritchard
Previous studies have prioritized trait-relevant cell types by looking for an enrichment of genome-wide association study (GWAS) signal within functional regions. However, these studies are limited in cell resolution by the lack of functional annotations from difficult-to-characterize or rare cell populations. Measurement of single-cell gene expression has become a popular method for characterizing novel cell types, and yet limited work has linked single-cell RNA sequencing (RNA-seq) to phenotypes of interest...
October 23, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29106805/innate-immunity-and-neurodegeneration
#12
Larisa I Labzin, Michael T Heneka, Eicke Latz
The innate immune system plays diverse roles in health and disease. It represents the first line of defense against infection and is involved in tissue repair, wound healing, and clearance of apoptotic cells and cellular debris. Excessive or nonresolving innate immune activation can lead to systemic or local inflammatory complications and cause or contribute to the development of inflammatory diseases. In the brain, microglia represent the key innate immune cells, which are involved in brain development, brain maturation, and homeostasis...
November 6, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/29101021/microglial-specific-transcriptome-changes-following-chronic-alcohol-consumption
#13
Gizelle M McCarthy, Sean P Farris, Yuri A Blednov, R Adron Harris, R Dayne Mayfield
Microglia are fundamentally important immune cells within the central nervous system (CNS) that respond to environmental challenges to maintain normal physiological processes. Alterations in steady-state cellular function and over-activation of microglia can facilitate the initiation and progression of neuropathological conditions such as Alzheimer's disease, Multiple Sclerosis, and Major Depressive Disorder. Alcohol consumption disrupts signaling pathways including both innate and adaptive immune responses that are necessary for CNS homeostasis...
October 31, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29099058/diverse-effects-of-an-acetylcholinesterase-inhibitor-donepezil-on-hippocampal-neuronal-death-after-pilocarpine-induced-seizure
#14
Jeong Hyun Jeong, Bo Young Choi, A Ra Kho, Song Hee Lee, Dae Ki Hong, Sang Hwon Lee, Sang Yup Lee, Hong Ki Song, Hui Chul Choi, Sang Won Suh
Epileptic seizures are short episodes of abnormal brain electrical activity. Many survivors of severe epilepsy display delayed neuronal death and permanent cognitive impairment. Donepezil is an acetylcholinesterase inhibitor and is an effective treatment agent for Alzheimer's disease. However, the role of donepezil in seizure-induced hippocampal injury remains untested. Temporal lobe epilepsy (TLE) was induced by intraperitoneal injection of pilocarpine (25 mg/kg). Donepezil (2.5 mg/kg/day) was administered by gavage in three different settings: (1) pretreatment for three days before the seizure; (2) for one week immediately after the seizure; and (3) for three weeks from three weeks after the seizure...
November 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29081415/cortical-iron-reflects-severity-of%C3%A2-alzheimer-s-disease
#15
Sara van Duijn, Marjolein Bulk, Sjoerd G van Duinen, Rob J A Nabuurs, Mark A van Buchem, Louise van der Weerd, Remco Natté
Abnormal iron distribution in the isocortex is increasingly recognized as an in vivo marker for Alzheimer's disease (AD). However, the contribution of iron accumulation to the AD pathology is still poorly understood. In this study, we investigated: 1) frontal cortical iron distribution in AD and normal aging and 2) the relation between iron distribution and degree of AD pathology. We used formalin fixed paraffin embedded frontal cortex from 10 AD patients, 10 elder, 10 middle aged, and 10 young controls and visualized iron with a modified Perl's histochemical procedure...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29078046/dendritic-polyglycerol-sulfates-in-the-prevention-of-synaptic-loss-and-mechanism-of-action-on-glia
#16
Dusica Maysinger, Jeff Ji, Alexandre Moquin, Shireen Hossain, Mark A Hancock, Issan Zhang, Philip K Y Chang, Matthew Rigby, Madeleine Anthonisen, Peter Grutter, John C S Breitner, R Anne McKinney, Sabine Reimann, Rainer Haag, Gerhard Multhaup
Dendritic polyglycerols (dPG), particularly dendritic polyglycerol sulfates (dPGS), have been intensively studied due to their intrinsic anti-inflammatory activity. As related to brain pathologies involving neuroinflammation, the current study examined if dPG and dPGS can (i) regulate neuroglial activation, and (ii) normalize the morphology and function of excitatory postsynaptic dendritic spines adversely affected by the neurotoxic 42 amino acid amyloid-β (Aβ42) peptide of Alzheimer disease (AD). The exact role of neuroglia, such as microglia and astrocytes, remains controversial especially their positive and negative impact on inflammatory processes in AD...
October 27, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29073081/trem2-deficiency-attenuates-neuroinflammation-and-protects-against-neurodegeneration-in-a-mouse-model-of-tauopathy
#17
Cheryl E G Leyns, Jason D Ulrich, Mary B Finn, Floy R Stewart, Lauren J Koscal, Javier Remolina Serrano, Grace O Robinson, Elise Anderson, Marco Colonna, David M Holtzman
Variants in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) were recently found to increase the risk for developing Alzheimer's disease (AD). In the brain, TREM2 is predominately expressed on microglia, and its association with AD adds to increasing evidence implicating a role for the innate immune system in AD initiation and progression. Thus far, studies have found TREM2 is protective in the response to amyloid pathology while variants leading to a loss of TREM2 function impair microglial signaling and are deleterious...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29070438/humanin-affects-object-recognition-and-gliosis-in-short-term-cuprizone-treated-mice
#18
Minetaka Murakami, Masatoshi Nagahama, Yoichiro Abe, Takako Niikura
Humanin (HN) is a 24-residue peptide that manipulates cell survival under various stresses. A highly potent HN derivative, HNG, reduced amyloid burden and neuroinflammation and suppressed cognitive impairment in Alzheimer's disease model mice. Cuprizone (CPZ), a copper chelator, provokes demyelination in the central nervous system of mice. A shorter (one week) exposure to CPZ induces schizophrenia-like behavior and glial activation prior to demyelination. We tested the effect of HNG on these short-term responses to CZP in mice...
October 14, 2017: Neuropeptides
https://www.readbyqxmd.com/read/29063348/differential-contribution-of-microglia-and-monocytes-in-neurodegenerative-diseases
#19
REVIEW
Caroline Baufeld, Elaine O'Loughlin, Narghes Calcagno, Charlotte Madore, Oleg Butovsky
Neuroinflammation is a hallmark of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Microglia, the innate immune cells of the CNS, are the first to react to pathological insults. However, multiple studies have also demonstrated an involvement of peripheral monocytes in several neurodegenerative diseases. Due to the different origins of these two cell types, it is important to distinguish their role and function in the development and progression of these diseases...
October 23, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29059594/the-age-related-slow-increase-in-amyloid-pathology-in-app-v717i-mice-activates-microglia-but-does-not-alter-hippocampal-neurogenesis
#20
Lianne Hoeijmakers, Gideon F Meerhoff, Janneke W de Vries, Silvie R Ruigrok, Anne-Marie van Dam, Fred van Leuven, Aniko Korosi, Paul J Lucassen
In Alzheimer's disease, the hippocampus is characterized by abundant deposition of amyloid peptides (amyloid β [Aβ]) and neuroinflammation. Adult hippocampal neurogenesis (AHN) is a form of plasticity that contributes to cognition and can be influenced by either or both pathology and neuroinflammation. Their interaction has been studied before in rapidly progressing transgenic mouse models with strong overexpression of amyloid precursor protein (APP) and/or presenilin 1. So far, changes in AHN and neuroinflammation remain poorly characterized in slower progressing models at advanced age, which approach more closely sporadic Alzheimer's disease...
September 22, 2017: Neurobiology of Aging
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