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Microglia alzheimer's disease

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https://www.readbyqxmd.com/read/29443098/a-novel-in-vitro-live-imaging-assay-of-astrocyte-mediated-phagocytosis-using-ph-indicator-conjugated-synaptosomes
#1
Youkyeong Gloria Byun, Won-Suk Chung
Astrocytes are the major cell type in the brain and directly contact synapses and blood vessels. Although microglial cells have been considered the major immune cells and only phagocytes in the brain, recent studies have shown that astrocytes also participate in various phagocytic processes, such as developmental synapse elimination and clearance of amyloid beta plaques in Alzheimer's disease (AD). Despite these findings, the efficiency of astrocyte engulfment and degradation of their targets is unclear compared with that of microglia...
February 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29427657/the-evolving-dialogue-of-microglia-and-neurons-in-alzheimer-s-disease-microglia-as-necessary-transducers-of-pathology
#2
REVIEW
E Simon, J Obst, D Gomez-Nicola
The understanding of the contribution of microglial cells to the onset and/or progression chronic neurodegenerative diseases is key to identify disease-modifying therapies, given the strong neuroimmune component of these disorders. In this review, we dissect the different pathways by which microglia can affect, directly or indirectly, neuronal function and dysfunction associated with diseases like Alzheimer's. We here present the rationale for proposing a model to explain the contribution of microglia to the pathophysiology of Alzheimer's disease, defining microglial cells as necessary transducers of pathology and ideal targets for intervention...
February 7, 2018: Neuroscience
https://www.readbyqxmd.com/read/29426702/high-dimensional-single-cell-mapping-of-central-nervous-system-immune-cells-reveals-distinct-myeloid-subsets-in-health-aging-and-disease
#3
Dunja Mrdjen, Anto Pavlovic, Felix J Hartmann, Bettina Schreiner, Sebastian G Utz, Brian P Leung, Iva Lelios, Frank L Heppner, Jonathan Kipnis, Doron Merkler, Melanie Greter, Burkhard Becher
Individual reports suggest that the central nervous system (CNS) contains multiple immune cell types with diverse roles in tissue homeostasis, immune defense, and neurological diseases. It has been challenging to map leukocytes across the entire brain, and in particular in pathology, where phenotypic changes and influx of blood-derived cells prevent a clear distinction between reactive leukocyte populations. Here, we applied high-dimensional single-cell mass and fluorescence cytometry, in parallel with genetic fate mapping systems, to identify, locate, and characterize multiple distinct immune populations within the mammalian CNS...
February 6, 2018: Immunity
https://www.readbyqxmd.com/read/29425372/sleep-deprivation-and-csf-biomarkers-for-alzheimer-disease
#4
Martin Olsson, Johan Ärlig, Jan Hedner, Kaj Blennow, Henrik Zetterberg
Study Objective: To investigate the cumulative effect of 5 consecutive nights of partial sleep deprivation on a panel of cerebrospinal fluid (CSF) biomarkers in healthy adults. Methods: A randomized, cross-over study conducted at the University of Gothenburg. The participants (N=13) were healthy adults (20-40 years of age) with a normal sleeping pattern. The participants underwent a baseline sleep period consisting of 5 nights with 8h spent in bed. A subsequent period with partial sleep deprivation (PSD) consisted of 5 nights of maximum 4h of sleep per night...
February 7, 2018: Sleep
https://www.readbyqxmd.com/read/29424844/dietary-lipophilic-iron-alters-amyloidogenesis-and-microglial-morphology-in-alzheimer-s-disease-knock-in-app-mice
#5
Douglas G Peters, Alexis N Pollack, Keith C Cheng, Dongxiao Sun, Takaomi Saido, Michael P Haaf, Qing X Yang, James R Connor, Mark D Meadowcroft
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized pathologically by amyloid beta (Aβ) deposition, microgliosis, and iron dyshomeostasis. Increased labile iron due to homeostatic dysregulation is believed to facilitate amyloidogenesis. Free iron is incorporated into aggregating amyloid peptides during Aβ plaque formation and increases potential for oxidative stress surrounding plaques. The goal of this work was to observe how brain iron levels temporally influence Aβ plaque formation, plaque iron concentration, and microgliosis...
February 9, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29423384/perspectives-in-lipocalin-2-emerging-biomarker-for-medical-diagnosis-and-prognosis-for-alzheimer-s-disease
#6
REVIEW
Juhyun Song, Oh Yoen Kim
Lipocalin-2 (LCN2), a secreted glycoprotein belonging to the lipocalin superfamily was reported to participate in various biological processes including cell migration, cell survival, inflammatory responses, and insulin sensitivity. LCN2 is expressed in the multiple tissues such as kidney, liver, uterus, and bone marrow. The receptors for LCN2 were additionally found in microglia, astrocytes, epithelial cells, and neurons, but the role of LCN2 in the central nervous system (CNS) has not been fully understood yet...
January 2018: Clinical Nutrition Research
https://www.readbyqxmd.com/read/29417448/atorvastatin-attenuates-cognitive-deficits-and-neuroinflammation-induced-by-a%C3%AE-1-42-involving-modulation-of-tlr4-traf6-nf-%C3%AE%C2%BAb-pathway
#7
Shan Wang, Xiaowei Zhang, Liuyu Zhai, Xiaona Sheng, Weina Zheng, Hongshan Chu, Guohua Zhang
Inflammatory damage aggravates the progression of Alzheimer's disease (AD) and the mechanism of inflammatory damage may provide a new therapeutic window for the treatment of AD. Toll-like receptor 4 (TLR4)-mediated signaling can regulate the inflammatory process. However, changes in TLR4 signaling pathway induced by beta-amyloid (Aβ) have not been well characterized in brain, especially in the hippocampus. In the present study, we explored the changes of TLR4 signaling pathway induced by Aβ in the hippocampus and the role of atorvastatin in modulating this signal pathway and neurotoxicity induced by Aβ...
February 7, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29416036/a-transcriptomic-atlas-of-aged-human-microglia
#8
Marta Olah, Ellis Patrick, Alexandra-Chloe Villani, Jishu Xu, Charles C White, Katie J Ryan, Paul Piehowski, Alifiya Kapasi, Parham Nejad, Maria Cimpean, Sarah Connor, Christina J Yung, Michael Frangieh, Allison McHenry, Wassim Elyaman, Vlad Petyuk, Julie A Schneider, David A Bennett, Philip L De Jager, Elizabeth M Bradshaw
With a rapidly aging global human population, finding a cure for late onset neurodegenerative diseases has become an urgent enterprise. However, these efforts are hindered by the lack of understanding of what constitutes the phenotype of aged human microglia-the cell type that has been strongly implicated by genetic studies in the pathogenesis of age-related neurodegenerative disease. Here, we establish the set of genes that is preferentially expressed by microglia in the aged human brain. This HuMi_Aged gene set captures a unique phenotype, which we confirm at the protein level...
February 7, 2018: Nature Communications
https://www.readbyqxmd.com/read/29413519/imaging-translocator-protein-as-a-biomarker-of-neuroinflammation-in-dementia
#9
William C Kreisl, Ioline D Henter, Robert B Innis
Neuroinflammation has long been considered a potential contributor to neurodegenerative disorders that result in dementia. Accumulation of abnormal protein aggregates in Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies is associated with the activation of microglia and astrocytes into proinflammatory states, and chronic low-level activation of glial cells likely contributes to the pathological changes observed in these and other neurodegenerative diseases. The 18kDa translocator protein (TSPO) is a key biomarker for measuring inflammation in the brain via positron emission tomography (PET)...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29411406/apoe-%C3%AE%C2%B54-is-also-required-in-trem2-r47h-variant-carriers-for-alzheimer-s-disease-to-develop
#10
Christina E Murray, Andrew King, Claire Troakes, Angela Hodges, Tammaryn Lashley
In late-onset Alzheimer's disease (AD), the ε4 allele of the apolipoprotein E gene (APOE) is the major known genetic risk factor [1]. In 2013 two research groups reported the R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2), is associated with AD by almost as much as APOE ε4 [2,3]. A loss-of-function R47H mutation in TREM2 is also one of the strongest single allele genetic risk factors for AD [2,3], providing a link between microglia dysfunction and AD pathogenesis. TREM2 encodes a single-pass type I membrane protein that forms a receptor-signaling complex with the TYRO protein tyrosine kinase-binding protein (TYROBP) triggering immune responses in certain macrophages and dendritic cells...
February 7, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29411111/functional-morphology-of-the-blood-brain-barrier-in-health-and-disease
#11
REVIEW
Stefan Liebner, Rick M Dijkhuizen, Yvonne Reiss, Karl H Plate, Dritan Agalliu, Gabriela Constantin
The adult quiescent blood-brain barrier (BBB), a structure organised by endothelial cells through interactions with pericytes, astrocytes, neurons and microglia in the neurovascular unit, is highly regulated but fragile at the same time. In the past decade, there has been considerable progress in understanding not only the molecular pathways involved in BBB development, but also BBB breakdown in neurological diseases. Specifically, the Wnt/β-catenin, retinoic acid and sonic hedgehog pathways moved into the focus of BBB research...
February 6, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29401686/evaluation-of-polyphenol-anthocyanin-enriched-extracts-of-blackberry-black-raspberry-blueberry-cranberry-red-raspberry-and-strawberry-for-free-radical-scavenging-reactive-carbonyl-species-trapping-anti-glycation-anti-%C3%AE-amyloid-aggregation-and-microglial-neuroprotective
#12
Hang Ma, Shelby L Johnson, Weixi Liu, Nicholas A DaSilva, Susan Meschwitz, Joel A Dain, Navindra P Seeram
Glycation is associated with several neurodegenerative disorders, including Alzheimer's disease (AD), where it potentiates the aggregation and toxicity of proteins such as β-amyloid (Aβ). Published studies support the anti-glycation and neuroprotective effects of several polyphenol-rich fruits, including berries, which are rich in anthocyanins. Herein, blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts were evaluated for: (1) total phenolic and anthocyanins contents, (2) free radical (DPPH) scavenging and reactive carbonyl species (methylglyoxal; MGO) trapping, (3) anti-glycation (using BSA-fructose and BSA-MGO models), (4) anti-Aβ aggregation (using thermal- and MGO-induced fibrillation models), and, (5) murine microglia (BV-2) neuroprotective properties...
February 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29399292/anti-neuroinflammatory-effects-of-ethanolic-extract-of-black-chokeberry-aronia-melanocapa-l-in-lipopolysaccharide-stimulated-bv2-cells-and-icr-mice
#13
Kang Pa Lee, Nan Hee Choi, Hyun-Soo Kim, Sanghyun Ahn, In-Sik Park, Dea Won Lee
BACKGROUND/OBJECTIVES: One of the mechanisms considered to be prevalent in the development of Alzheimer's disease (AD) is hyper-stimulation of microglia. Black chokeberry (Aronia melanocapa L.) is widely used to treat diabetes and atherosclerosis, and is known to exert anti-oxidant and anti-inflammatory effects; however, its neuroprotective effects have not been elucidated thus far. MATERIALS/METHODS: We undertook to assess the anti-inflammatory effect of the ethanolic extract of black chokeberry friut (BCE) in BV2 cells, and evaluate its neuroprotective effect in the lipopolysaccharide (LPS)-induced mouse model of AD...
February 2018: Nutrition Research and Practice
https://www.readbyqxmd.com/read/29396107/oligomeric-amyloid-%C3%AE-preferentially-targets-neuronal-and-not-glial-mitochondrial-encoded-mrnas
#14
Diego Mastroeni, Jennifer Nolz, Omar M Khdour, Shobana Sekar, Elaine Delvaux, Lori Cuyugan, Winnie S Liang, Sidney M Hecht, Paul D Coleman
INTRODUCTION: Our laboratories have demonstrated that accumulation of oligomeric amyloid β (OAβ) in neurons is an essential step leading to OAβ-mediated mitochondrial dysfunction. METHODS: Alzheimer's disease (AD) and matching control hippocampal neurons, astrocytes, and microglia were isolated by laser-captured microdissection from the same subjects, followed by whole-transcriptome sequencing. Complementary in vitro work was performed in OAβ-treated differentiated SH-SY5Y, followed by the use of a novel CoQ10 analogue for protection...
January 20, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29391235/novel-targets-in-alzheimer-s-disease-a-special-focus-on-microglia
#15
REVIEW
Claudia Balducci, Gianluigi Forloni
Several years after the intriguing novelty in the β-amyloid (Aβ) cascade hypothesis, where the Aβ oligomers emerged as the most detrimental species in the neuropathogenic process of Alzheimer's disease (AD) in place of fibrillar plaques, more recently innate immune system have come on stage as the other prominent factor. Neuroinflammation apparently contributes to AD eziopathogenesis, in large part through overactivation of microglia cells. Genetic and experimental studies strongly support the contribution of the immune system to increasing the risk of AD and participating in its progression...
January 30, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29382415/-fasudil-improves-cognition-of-app-ps1-transgenic-mice-via-inhibiting-the-activation-of-microglia-and-shifting-microglia-phenotypes-from-m1-to-m2
#16
Jiezhong Yu, Qingfang Gu, Yuqing Yan, Hongqiang Yu, Minfang Guo, Chunyun Liu, Guobin Song, Zhi Chai, Qing Wang, Baoguo Xiao, Hanting Zhang, Yuqiang Jiang, Cungen Ma
Objective To examine the regulatory effects of Rho kinase inhibitor fasudil on cognition and microglia polarization in APP/PS1 transgenic (APP/PS1 Tg) mice, a widely used model of Alzheimer's disease (AD). Methods Male APP/PS1 Tg mice at 8 months of age were randomly divided into two groups: Fasudil (25 mg/kg) and saline, i.p., once daily for 2 months; age- and gender-matched wild type (WT) mice without treatment were used as the controls. The Morris water maze (MWM) test was applied to examine spatial cognition of mice...
December 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29378960/lysosomal-enzyme-tripeptidyl-peptidase-1-destabilizes-fibrillar-a%C3%AE-by-multiple-endoproteolytic-cleavages-within-the-%C3%AE-sheet-domain
#17
Santiago Solé-Domènech, Ana V Rojas, Gia G Maisuradze, Harold A Scheraga, Peter Lobel, Frederick R Maxfield
Accumulation of amyloid-beta (Aβ), which is associated with Alzheimer's disease, can be caused by excess production or insufficient clearance. Because of its β-sheet structure, fibrillar Aβ is resistant to proteolysis, which would contribute to slow degradation of Aβ plaques in vivo. Fibrillar Aβ can be internalized by microglia, which are the scavenger cells of the brain, but the fibrils are degraded only slowly in microglial lysosomes. Cathepsin B is a lysosomal protease that has been shown to proteolyze fibrillar Aβ...
January 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29376871/retinoic-acid-enhances-apolipoprotein-e-synthesis-in-human-macrophages
#18
Vera Clemens, Francesca Regen, Nathalie Le Bret, Isabella Heuser, Julian Hellmann-Regen
Apolipoprotein E (ApoE) represents a pivotal target in Alzheimer's disease (AD) and is modulated through retinoic acid (RA), an endogenous neuroprotective and anti-inflammatory compound. A major source of ApoE are microglia, which are pathologically activated in AD. Activated microglia are known to block RA signaling. This suggests a vicious cycle between inflammation, RA signaling, and ApoE homeostasis in AD pathogenesis. To test this hypothesis, we investigated effects of RA and proinflammatory activation on ApoE synthesis in primary human macrophage-derived microglial-like cells...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29376849/progression-of-alzheimer-s-disease-related-pathology-and-cell-counts-in-a-patient-with-idiopathic-normal-pressure-hydrocephalus
#19
Sylwia Libard, Katarina Laurell, Kristina Giuliana Cesarini, Irina Alafuzoff
We had an opportunity to assess the change observed in the brain regarding Alzheimer's disease (AD)-related alterations, cell count, and inflammation that took place during a period of 21 months in a subject with a definite diagnosis of AD and idiopathic Normal Pressure Hydrocephalus (iNPH). Four neuronal markers, i.e., synaptophysin, microtubule associated protein 2, non-phosphorylated neurofilament H (SMI32), and embryonic lethal abnormal visual system proteins 3/4 HuC/HuD (HuC/HuD); three microglial markers CD68, Human Leucocytic Antigen DR, ionized calcium-binding adaptor molecule 1, glial fibrillary acidic protein (GFAP); and AD-related markers, hyperphosphorylated τ (HPτ) and amyloid-β (Aβ, Aβ40, Aβ42) were assessed...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29365370/candesartan-ameliorates-brain-inflammation-associated-with-alzheimer-s-disease
#20
Nofar Torika, Keren Asraf, Ron N Apte, Sigal Fleisher-Berkovich
AIMS: Alzheimer's disease (AD) pathology is associated with brain inflammation involving microglia and astrocytes. The renin-angiotensin system contributes to brain inflammation associated with AD pathology. This study aimed to investigate the role of candesartan, an angiotensin II type 1 receptor blocker, in modulation of glial functions associated with AD. METHODS: Focusing on the role of candesartan in glial inflammation, we evaluated inflammatory mediators' levels, secreted by lipopolysaccharide-induced microglia following candesartan treatment...
January 24, 2018: CNS Neuroscience & Therapeutics
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