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Amyloid aging microglia

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https://www.readbyqxmd.com/read/27878757/targeting-ccr3-to-reduce-amyloid-%C3%AE-production-tau-hyperphosphorylation-and-synaptic-loss-in-a-mouse-model-of-alzheimer-s-disease
#1
Chunyan Zhu, Bing Xu, Xiaohong Sun, Qiwen Zhu, Yi Sui
The majority of Alzheimer's disease (AD) patients have a late onset, and chronic neuroinflammation, characterized by glial activation and secretion of pro-inflammatory cytokines and chemokines, plays a role in the pathogenesis of AD. The chemokine CCL11 has been shown to be a causative factor of cognitive decline in the process of aging, but little is known whether it is involved in the pathogenesis of AD. In the present study, we showed that CCR3, the receptor for CCL11, was expressed by hippocampal neurons and treatment of primary hippocampal neuronal cultures (14 days in vitro) with CCL11 resulted in activation of cyclin-dependent kinase 5 and glycogen synthase kinase-3β, associated with elevated tau phosphorylation at multiple sites...
November 23, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27830533/analysis-of-the-impact-of-cd200-on-phagocytosis
#2
Anthony Lyons, Aedín M Minogue, Raasay S Jones, Orla Fitzpatrick, Janis Noonan, Veronica A Campbell, Marina A Lynch
One factor that impacts on microglial activation is the interaction between the ubiquitously expressed CD200 and CD200R, which is expressed only on microglia in the brain. Decreased signalling through CD200R, when CD200 expression is reduced, results in microglial activation and may, at least in part, explain the increased cell activity that is observed with age, in models of Alzheimer's and Parkinson's disease as well as in the human diseases. There is evidence of increased microglial activation in CD200-deficient mice, and isolated microglia prepared from these mice are more reactive to inflammatory stimuli like Toll-like receptor 2 and 4 agonists, and interferon-γ...
November 9, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27814300/role-of-suppressor-of-cytokine-signaling-3-socs3-in-altering-activated-microglia-phenotype-in-appswe-ps1de9-mice
#3
Naotoshi Iwahara, Shin Hisahara, Jun Kawamata, Akihiro Matsumura, Kazuki Yokokawa, Taro Saito, Mai Fujikura, Tatsuo Manabe, Hiromi Suzuki, Takashi Matsushita, Syuuichirou Suzuki, Shun Shimohama
In response to changes of the central nervous system environment, microglia are capable of acquiring diverse phenotypes for cytotoxic or immune regulation and resolution of injury. Alzheimer's disease (AD) pathology also induces several microglial activations, resulting in production of pro-inflammatory cytokines and reactive oxygen species or clearance of amyloid-β (Aβ) through phagocytosis. We previously demonstrated that microglial activation and increase in oxidative stress started from the middle age in APPswe/PS1dE9 mice, and hypothesized that M1 activation occurs in middle-aged AD mice by Aβ stimulation...
November 3, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27805590/assessing-retinal-microglial-phagocytic-function-in-vivo-using-a-flow-cytometry-based-assay
#4
Salome Murinello, Stacey K Moreno, Matthew S Macauley, Susumu Sakimoto, Peter D Westenskow, Martin Friedlander
Microglia are the tissue resident macrophages of the central nervous system (CNS) and they perform a variety of functions that support CNS homeostasis, including phagocytosis of damaged synapses or cells, debris, and/or invading pathogens. Impaired phagocytic function has been implicated in the pathogenesis of diseases such as Alzheimer's and age-related macular degeneration, where amyloid-β plaque and drusen accumulate, respectively. Despite its importance, microglial phagocytosis has been challenging to assess in vivo...
October 18, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27775040/reac-technology-modifies-pathological-neuroinflammation-and-motor-behaviour-in-an-alzheimer-s-disease-mouse-model
#5
Lorenzini Luca, Giuliani Alessandro, Sivilia Sandra, Baldassarro Vito Antonio, Fernandez Mercedes, Lotti Margotti Matteo, Giardino Luciana, Fontani Vania, Rinaldi Salvatore, Calzà Laura
The search for new therapeutic approaches to Alzheimer disease (AD) is a major goal in medicine and society, also due to the impressive economic and social costs of this disease. In this scenario, biotechnologies play an important role. Here, it is demonstrated that the Radio Electric Asymmetric Conveyer (REAC), an innovative technology platform for neuro- and bio-modulation, used according to the neuro-regenerative protocol (RGN-N), significantly increases astroglial reaction around the amyloid plaques in an AD mouse model, as evaluated by GFAP-immunoreactivity, and reduces microglia-associated neuroinflammation markers, as evaluated by Iba1-immunoreactivity and mRNA expression level of inflammatory cytokines TREM...
October 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27723233/distinct-inflammatory-phenotypes-of-microglia-and-monocyte-derived-macrophages-in-alzheimer-s-disease-models-effects-of-aging-and-amyloid-pathology
#6
Elodie Martin, Céline Boucher, Bertrand Fontaine, Cécile Delarasse
Alzheimer's disease (AD) is a neurodegenerative disease characterized by formation of amyloid-β (Aβ) plaques, activated microglia, and neuronal cell death leading to progressive dementia. Recent data indicate that microglia and monocyte-derived macrophages (MDM) are key players in the initiation and progression of AD, yet their respective roles remain to be clarified. As AD occurs mostly in the elderly and aging impairs myeloid functions, we addressed the inflammatory profile of microglia and MDM during aging in TgAPP/PS1 and TgAPP/PS1dE9, two transgenic AD mouse models, compared to WT littermates...
October 8, 2016: Aging Cell
https://www.readbyqxmd.com/read/27718173/neuroinflammation-immune-system-and-alzheimer-disease-searching-for-the-missing-link
#7
F Guerriero, C Sgarlata, M Francis, N Maurizi, A Faragli, S Perna, M Rondanelli, M Rollone, G Ricevuti
Due to an increasingly aging population, Alzheimer disease (AD) represents a crucial issue for the healthcare system because of its widespread prevalence and the burden of its care needs. Several hypotheses on AD pathogenesis have been proposed and current therapeutical strategies have shown limited effectiveness. In the last decade, more evidence has supported a role for neuroinflammation and immune system dysregulation in AD. It remains unclear whether astrocytes, microglia and immune cells influence disease onset, progression or both...
October 7, 2016: Aging Clinical and Experimental Research
https://www.readbyqxmd.com/read/27688126/brain-omega-3-polyunsaturated-fatty-acids-modulate-microglia-cell-number-and-morphology-in-response-to-intracerebroventricular-amyloid-%C3%AE-1-40-in-mice
#8
Kathryn E Hopperton, Marc-Olivier Trépanier, Vanessa Giuliano, Richard P Bazinet
BACKGROUND: Neuroinflammation is a proposed mechanism by which Alzheimer's disease (AD) pathology potentiates neuronal death and cognitive decline. Consumption of omega-3 polyunsaturated fatty acids (PUFA) is associated with a decreased risk of AD in human observational studies and exerts protective effects on cognition and pathology in animal models. These fatty acids and molecules derived from them are known to have anti-inflammatory and pro-resolving properties, presenting a potential mechanism for these protective effects...
September 29, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27641666/microglial-response-to-lps-increases-in-wild-type-mice-during-aging-but-diminishes-in-an-alzheimer-s-mouse-model-implication-of-tlr4-signaling-in-disease-progression
#9
Michelle Go, Jinghong Kou, Jeong-Eun Lim, Junling Yang, Ken-Ichiro Fukuchi
Microglia-mediated clearance of amyloid beta-protein (Aβ) via Toll-like receptor 4 (TLR4) signaling may play an important role in the pathogenesis of Alzheimer's disease (AD). However, as the disease progresses, activated microglia appear to become incapable of clearing Aβ deposits. Because repeated exposure to a TLR4 ligand leads to a diminished response of monocytes/macrophages to lipopolysaccharide (LPS) and because aggregated Aβ is a TLR4 ligand, we hypothesize that chronic exposure of microglia to Aβ deposits may induce a state of Toll-like receptor (TLR) signaling dysfunction, leading to decreased Aβ clearance and accelerated disease progression...
October 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27577739/soluble-neuregulin-1-from-microglia-enhances-amyloid-beta-induced-neuronal-death
#10
Hyunjeong Liew, Yun-Mi Kim, Hee Soon Choi, Ah Ram Jang, David Churchill, Sang Hyung Lee, Yoo-Hun Suh
Neuregulin-1 (NRG-1) is a ligand of the epidermal growth factor receptor (erbB), and its interaction involves activation of the glutamatergic N-methyl-D-aspartate receptor, which increases the expression of the β2 subunit of the γ-aminobutyric acid receptor and subunits of the nicotinic acetylcholine receptor. In the dentate gyrus of 14-month-old Tg2576 mice, NRG-1 was strongly expressed compared with age-matched controls. The supernatant of oligomeric amyloid β peptide (Aβ42)-treated glial cells enhanced the Aβ42-induced cytotoxic effects, but the expression of Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand in microglial cells was not changed upon cytotoxic treatment...
August 15, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27567845/postmortem-adult-human-microglia-proliferate-in-culture-to-high-passage-and-maintain-their-response-to-amyloid-%C3%AE
#11
Ling Guo, Aras Rezvanian, Lokesh Kukreja, Ramez Hoveydai, Eileen H Bigio, M-Marsel Mesulam, Joseph El Khoury, Changiz Geula
Microglia are immune cells of the brain that display a range of functions. Most of our knowledge about microglia biology and function is based on cells from the rodent brain. Species variation in the complexity of the brain and differences in microglia response in the primate when compared with the rodent, require use of adult human microglia in studies of microglia biology. While methods exist for isolation of microglia from postmortem human brains, none allow culturing cells to high passage. Thus cells from the same case could not be used in parallel studies and multiple conditions...
October 4, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27453234/amyloid-%C3%AE-protein-aggravates-neuronal-senescence-and-cognitive-deficits-in-5xfad-mouse-model-of-alzheimer-s-disease
#12
Zhen Wei, Xiao-Chun Chen, Yue Song, Xiao-Dong Pan, Xiao-Man Dai, Jing Zhang, Xiao-Li Cui, Xi-Lin Wu, Yuan-Gui Zhu
BACKGROUND: Amyloid β (Aβ) has been established as a key factor for the pathological changes in the brains of patients with Alzheimer's disease (AD), and cellular senescence is closely associated with aging and cognitive impairment. However, it remains blurred whether, in the AD brains, Aβ accelerates the neuronal senescence and whether this senescence, in turn, impairs the cognitive function. This study aimed to explore the expression of senescence-associated genes in the hippocampal tissue from young to aged 5XFAD mice and their age-matched wild type (WT) mice to determine whether senescent neurons are present in the transgenic AD mouse model...
August 5, 2016: Chinese Medical Journal
https://www.readbyqxmd.com/read/27448243/all-trans-retinoic-acid-improved-impaired-proliferation-of-neural-stem-cells-and-suppressed-microglial-activation-in-the-hippocampus-in-an-alzheimer-s-mouse-model
#13
Risa Takamura, Naoto Watamura, Miyu Nikkuni, Toshio Ohshima
Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by cognitive impairment with neuronal loss. The number of patients suffering from AD has increased, but none of the present therapies stops the progressive symptoms in patients with AD. It has been reported that the activation of microglial cells induces harmful chronic inflammation, leading to neuronal death. Furthermore, the impairment of adult neurogenesis in the hippocampus has been observed earlier than amyloid plaque formation...
July 22, 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27444354/tenascin-c-is-associated-with-cored-amyloid-%C3%AE-plaques-in-alzheimer-disease-and-pathology-burdened-cognitively-normal-elderly
#14
Zhiping Mi, Willi Halfter, Eric E Abrahamson, William E Klunk, Chester A Mathis, Elliott J Mufson, Milos D Ikonomovic
Tenascin-C (TN-C) is an extracellular matrix glycoprotein linked to inflammatory processes in pathological conditions including Alzheimer disease (AD). We examined the distribution of TN-C immunoreactivity (ir) in relation to amyloid-β (Aβ) plaques and vascular Aβ deposits in autopsy brain tissues from 14 patients with clinical and neuropathological AD and 10 aged-matched controls with no cognitive impairment; 5 of the controls had Aβ plaques and 5 did not. TN-C ir was abundant in cortical white matter and subpial cerebral gray matter in all cases, whereas TN-C ir was weak in blood vessels...
September 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27425620/three-dimensional-study-of-alzheimer-s-disease-hallmarks-using-the-idisco-clearing-method
#15
Thomas Liebmann, Nicolas Renier, Karima Bettayeb, Paul Greengard, Marc Tessier-Lavigne, Marc Flajolet
Amyloidosis is a major problem in over one hundred diseases, including Alzheimer's disease (AD). Using the iDISCO visualization method involving targeted molecular labeling, tissue clearing, and light-sheet microscopy, we studied plaque formation in the intact AD mouse brain at up to 27 months of age. We visualized amyloid plaques in 3D together with tau, microglia, and vasculature. Volume imaging coupled to automated detection and mapping enables precise and fast quantification of plaques within the entire intact mouse brain...
July 26, 2016: Cell Reports
https://www.readbyqxmd.com/read/27425031/transcriptional-profiling-of-cd11c-positive-microglia-accumulating-around-amyloid-plaques-in-a-mouse-model-for-alzheimer-s-disease
#16
Willem Kamphuis, Lieneke Kooijman, Sjoerd Schetters, Marie Orre, Elly M Hol
Amyloid plaques in Alzheimer's disease (AD) mice are surrounded by activated microglia. The functional role of microglia activation in AD is not well understood; both detrimental and beneficial effects on AD progression have been reported. Here we show that the population of activated microglia in the cortex of the APPswe/PS1dE9 mouse AD model is divided into a CD11c-positive and a CD11c-negative subpopulation. Cd11c transcript levels and number of CD11c-positive microglia increase sharply when plaques start to occur and both parameters continue to rise in parallel with the age-related increasing plaque load...
October 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27421577/the-endocytic-pathway-in-microglia-during-health-aging-and-alzheimer-s-disease
#17
REVIEW
Santiago Solé-Domènech, Dana L Cruz, Estibaliz Capetillo-Zarate, Frederick R Maxfield
Microglia, the main phagocytes of the central nervous system (CNS), are involved in the surveillance and maintenance of nervous tissue. During normal tissue homeostasis, microglia migrates within the CNS, phagocytose dead cells and tissue debris, and modulate synapse pruning and spine formation via controlled phagocytosis. In the event of an invasion by a foreign body, microglia are able to phagocytose the invading pathogen and process it proteolytically for antigen presentation. Internalized substrates are incorporated and sorted within the endocytic pathway and thereafter transported via complex vesicular routes...
December 2016: Ageing Research Reviews
https://www.readbyqxmd.com/read/27369450/probing-amyloid-beta-induced-cell-death-using-a-fluorescence-peptide-conjugate-in-alzheimer-s-disease-mouse-model
#18
Jong Kil Lee, Kai Wang, Min Hee Park, Namoh Kim, Ju Youn Lee, Hee Kyung Jin, In-San Kim, Byung-Heon Lee, Jae-Sung Bae
With the increasing worldwide incidence of Alzheimer's disease (AD), there is a critical need for the discovery of more effective diagnostic methods. However, development of diagnostic tools in AD has been hindered by obstacles such as the absence of exact biomarkers. Apoptosis caused by amyloid-β (Aβ) plays an important role in AD pathology; therefore, provides an attractive biological target for the diagnosis of AD. The present study aimed to evaluate the potential of small peptide, named ApoPep-1 (Apoptosis-targeting peptide-1) as a new apoptosis imaging agent in AD...
September 1, 2016: Brain Research
https://www.readbyqxmd.com/read/27339073/increased-tauopathy-drives-microglia-mediated-clearance-of-beta-amyloid
#19
Wesley Chen, Edsel A Abud, Stephen T Yeung, Anita Lakatos, Trevor Nassi, Jane Wang, David Blum, Luc Buée, Wayne W Poon, Mathew Blurton-Jones
Alzheimer disease is characterized by the accumulation of β-amyloid (Aβ) plaques and tau-laden neurofibrillary tangles. Emerging studies suggest that in neurodegenerative diseases, aggregation of one protein species can promote other proteinopathies and that inflammation plays an important role in this process. To study the interplay between Aβ deposition, tau pathology, and microgliosis, we established a new AD transgenic mouse model by crossing 5xfAD mice with Thy-Tau22 transgenic mice. The resulting 'T5x' mice exhibit a greater than three-fold increase in misfolded and hyperphosphorylated tau and further substantiates the hypothesis that Aβ accelerates tau pathology...
2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27277332/upregulation-of-microrna-206-enhances-lipopolysaccharide-induced-inflammation-and-release-of-amyloid-%C3%AE-by-targeting-insulin-like-growth-factor%C3%A2-1-in-microglia
#20
Hongxia Xing, Shuangxi Guo, Yi Zhang, Zhiyong Zheng, Haoliang Wang
Activated microglia are capable of facilitating amyloid-β (Aβ) accumulation via the release of inflammatory factors, thus resulting in the exacerbation of Alzheimer's disease (AD). MicroRNAs (miRs) participate in the activation of microglia, which is associated with AD. Insulin-like growth factor 1 (IGF1) is a neuroprotective, anti-inflammatory factor, which is able to accelerate clearance of Aβ peptides. The present study aimed to investigate the precise role of miR‑206 and IGF1 in lipopolysaccharide (LPS)‑induced microglial inflammation...
August 2016: Molecular Medicine Reports
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