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Microglia alzheimer's disease

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https://www.readbyqxmd.com/read/28434692/immune-hyperreactivity-of-a%C3%AE-plaque-associated-microglia-in-alzheimer-s-disease
#1
Zhuoran Yin, Divya Raj, Nasrin Saiepour, Debby Van Dam, Nieske Brouwer, Inge R Holtman, Bart J L Eggen, Thomas Möller, Joseph A Tamm, Aicha Abdourahman, Elly M Hol, Willem Kamphuis, Thomas A Bayer, Peter P De Deyn, Erik Boddeke
Alzheimer's disease (AD) is strongly associated with microglia-induced neuroinflammation. Particularly, Aβ plaque-associated microglia take on an "activated" morphology. However, the function and phenotype of these Aβ plaque-associated microglia are not well understood. We show hyperreactivity of Aβ plaque-associated microglia upon systemic inflammation in transgenic AD mouse models (i.e., 5XFAD and APP23). Gene expression profiling of Aβ plaque-associated microglia (major histocompatibility complex II(+) microglia) isolated from 5XFAD mice revealed a proinflammatory phenotype...
March 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28431620/role-of-inflammatory-molecules-in-the-alzheimer-s-disease-progression-and-diagnosis
#2
REVIEW
Eva Bagyinszky, Vo Van Giau, Kyuhwan Shim, Kyoungho Suk, Seong Soo A An, SangYun Kim
Alzheimer's disease (AD) is a complex disorder and the most common form of neurodegenerative dementia. Several genetic, environmental, and physiological factors, including inflammations and metabolic influences, are involved in the progression of AD. Inflammations are composed of complicated networks of many chemokines and cytokines with diverse cells. Inflammatory molecules are needed for the protection against pathogens, and maintaining their balances is important for normal physiological function. Recent studies demonstrated that inflammation may be involved in neurodegenerative dementia...
May 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28427563/neuroinflammation-in-alzheimer-s-disease-the-preventive-and-therapeutic-potential-of-polyphenolic-nutraceuticals
#3
Yousef Sawikr, Nagendra Sastry Yarla, Ilaria Peluso, Mohammad Amjad Kamal, Gjumrakch Aliev, Anupam Bishayee
Brain inflammation, characterized by increased microglia and astrocyte activation, increases during aging and is a key feature of neurodegenerative diseases, such as Alzheimer's disease (AD). In AD, neuronal death and synaptic impairment, induced by amyloid-β (Aβ) peptide, are at least in part mediated by microglia and astrocyte activation. Glial activation results in the sustained production of proinflammatory cytokines and reactive oxygen species, giving rise to a chronic inflammatory process. Astrocytes are the most abundant glial cells in the central nervous system and are involved in the neuroinflammation...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28426964/ipsc-derived-human-microglia-like-cells-to-study-neurological-diseases
#4
Edsel M Abud, Ricardo N Ramirez, Eric S Martinez, Luke M Healy, Cecilia H H Nguyen, Sean A Newman, Andriy V Yeromin, Vanessa M Scarfone, Samuel E Marsh, Cristhian Fimbres, Chad A Caraway, Gianna M Fote, Abdullah M Madany, Anshu Agrawal, Rakez Kayed, Karen H Gylys, Michael D Cahalan, Brian J Cummings, Jack P Antel, Ali Mortazavi, Monica J Carson, Wayne W Poon, Mathew Blurton-Jones
Microglia play critical roles in brain development, homeostasis, and neurological disorders. Here, we report that human microglial-like cells (iMGLs) can be differentiated from iPSCs to study their function in neurological diseases, like Alzheimer's disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo, and whole-transcriptome analysis demonstrates that they are highly similar to cultured adult and fetal human microglia. Functional assessment of iMGLs reveals that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28420415/distribution-pattern-following-systemic-mesenchymal-stem-cell-injection-depends-on-the-age-of-the-recipient-and-neuronal-health
#5
Claire Fabian, Yahaira Naaldijk, Christiane Leovsky, Adiv A Johnson, Lukas Rudolph, Carsten Jaeger, Katrin Arnold, Alexandra Stolzing
BACKGROUND: Mesenchymal stem cells (MSCs) show therapeutic efficacy in many different age-related degenerative diseases, including Alzheimer's disease. Very little is currently known about whether or not aging impacts the transplantation efficiency of MSCs. METHODS: In this study, we investigated the distribution of intravenously transplanted syngeneic MSCs derived from young and aged mice into young, aged, and transgenic APP/PS1 Alzheimer's disease mice. MSCs from male donors were transplanted into female mice and their distribution pattern was monitored by PCR using Y-chromosome specific probes...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28413987/alzheimer-s-disease-like-early-phase-brain-pathogenesis-self-curing-amelioration-of-neurodegeneration-from-pro-inflammatory-wounding-to-anti-inflammatory-healing
#6
Jiang He, Tao Liao, Guo-Xin Zhong, Ji-Da Zhang, Yan-Ping Chen, Qi Wang, Qing-Ping Zeng
The etiological initiators of neuroinflammation remain inclusive, and effective interventions to block neurodegeneration are unavailable. Surprisingly, we found collagen II-combined complete Freund's adjuvant (CC) that usually induces rheumatoid arthritis (RA) also drives Alzheimer's disease (AD)-like neurodegeneration in mice. CC not only upregulates the cerebral pro-inflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukin 8 (IL-8), but also downregulates the cerebral interleukin 10 (IL-10), an anti-inflammatory cytokine, and tyrosine hydroxylase (TH), a rate-limiting enzyme for biosynthesis of the anti-inflammatory neurotransmitter dopamine...
April 17, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28409032/distinct-pattern-of-microgliosis-in-the-olfactory-bulb-of-neurodegenerative-proteinopathies
#7
Zacharias Kohl, Johannes C M Schlachetzki, Judith Feldewerth, Philipp Hornauer, Martina Münch, Anthony Adame, Markus J Riemenschneider, Jürgen Winkler, Eliezer Masliah
The olfactory bulb (OB) shows early neuropathological hallmarks in numerous neurodegenerative diseases, for example, in Alzheimer's disease (AD) and Parkinson's disease (PD). The glomerular and granular cell layer of the OB is characterized by preserved cellular plasticity in the adult brain. In turn, alterations of this cellular plasticity are related to neuroinflammation such as microglia activation, implicated in the pathogenesis of AD and PD, as well as frontotemporal lobe degeneration (FTLD). To determine microglia proliferation and activation we analyzed ionized calcium binding adaptor molecule 1 (Iba1) expressing microglia in the glomerular and granular cell layer, and the olfactory tract of the OB from patients with AD, PD dementia/dementia with Lewy bodies (PDD/DLB), and FTLD compared to age-matched controls...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28404595/nlr-members-nlrc4-and-nlrp3-mediate-sterile-inflammasome-activation-in-microglia-and-astrocytes
#8
Leslie Freeman, Haitao Guo, Clément N David, W June Brickey, Sushmita Jha, Jenny P-Y Ting
Inflammation in the brain accompanies several high-impact neurological diseases including multiple sclerosis (MS), stroke, and Alzheimer's disease. Neuroinflammation is sterile, as damage-associated molecular patterns rather than microbial pathogens elicit the response. The inflammasome, which leads to caspase-1 activation, is implicated in neuroinflammation. In this study, we reveal that lysophosphatidylcholine (LPC), a molecule associated with neurodegeneration and demyelination, elicits NLRP3 and NLRC4 inflammasome activation in microglia and astrocytes, which are central players in neuroinflammation...
April 12, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28398520/injury-leads-to-the-appearance-of-cells-with-characteristics-of-both-microglia-and-astrocytes-in-mouse-and-human-brain
#9
Ulrika Wilhelmsson, Daniel Andersson, Yolanda de Pablo, Roy Pekny, Anders Ståhlberg, Jan Mulder, Nicholas Mitsios, Tibor Hortobágyi, Milos Pekny, Marcela Pekna
Microglia and astrocytes have been considered until now as cells with very distinct identities. Here, we assessed the heterogeneity within microglia/monocyte cell population in mouse hippocampus and determined their response to injury, by using single-cell gene expression profiling of cells isolated from uninjured and deafferented hippocampus. We found that in individual cells, microglial markers Cx3cr1, Aif1, Itgam, and Cd68 were co-expressed. Interestingly, injury led to the co-expression of the astrocyte marker Gfap in a subpopulation of Cx3cr1-expressing cells from both the injured and contralesional hippocampus...
April 7, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28397068/amniotic-mesenchymal-stem-cells-decrease-a%C3%AE-deposition-and-improve-memory-in-app-ps1-transgenic-mice
#10
Xiao-Yu Zheng, Qian-Quan Wan, Chuan-Yi Zheng, Hong-Long Zhou, Xing-Yu Dong, Qing-Shan Deng, Hui Yao, Qiang Fu, Mou Gao, Zhong-Jie Yan, Shan-Shan Wang, Yu You, Jun Lv, Xiang-Yu Wang, Ke-En Chen, Mao-Ying Zhang, Ru-Xiang Xu
Transplantation of human amniotic mesenchymal stem cells (hAM-MSCs) seems to be a promising strategy for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, the clinical therapeutic effects of hAM-MSCs and their mechanisms of action in AD remain to be determined. Here, we used amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice to evaluate the effects of hAM-MSC transplantation on AD-related neuropathology and cognitive dysfunction. We found that hAM-MSC transplantation into the hippocampus dramatically reduced amyloid-β peptide (Aβ) deposition and rescued spatial learning and memory deficits in APP/PS1 mice...
April 10, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28390825/changes-in-cd200-and-intercellular-adhesion-molecule-1-icam-1-levels-in-brains-of-lewy-body-disorder-cases-are-associated-with-amounts-of-alzheimer-s-pathology-not-%C3%AE-synuclein-pathology
#11
Douglas G Walker, Lih-Fen Lue, Tiffany M Tang, Charles H Adler, John N Caviness, Marwan N Sabbagh, Geidy E Serrano, Lucia I Sue, Thomas G Beach
Enhanced inflammation has been associated with Alzheimer's disease (AD) and diseases with Lewy body (LB) pathology, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). One issue is whether amyloid and tangle pathology, features of AD, or α-synuclein LB pathology have similar or different effects on brain inflammation. An aim of this study was to examine if certain features of inflammation changed in brains with increasing LB pathology. To assess this, we measured levels of the anti-inflammatory protein CD200 and the pro-inflammatory protein intercellular adhesion molecule-1 (ICAM-1) in cingulate and temporal cortex from a total of 143 cases classified according to the Unified Staging System for LB disorders...
June 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28387679/orexin-impairs-the-phagocytosis-and-degradation-of-amyloid-%C3%AE-fibrils-by-microglial-cells
#12
Hoyoung An, Mi-Hyang Cho, Dong-Hou Kim, Seockhoon Chung, Seung-Yong Yoon
BACKGROUND: Intracranial accumulation of amyloid-β (Aβ) is a characteristic finding of Alzheimer's disease (AD). It is thought to be the result of Aβ overproduction by neurons and impaired clearance by several systems, including degradation by microglia. Sleep disturbance is now considered a risk factor for AD, but studies focusing on how sleep modulates microglial handling of Aβ have been scarce. OBJECTIVE: To determine whether phagocytosis and degradation of extracellular Aβ fibrils by BV2 microglial cells were impaired by treatment with orexin-A/B, a major modulator of the sleep-wake cycle, which may mimic sleep deprivation conditions...
April 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28386767/increased-quinolinic-acid-in-peripheral-mononuclear-cells-in-alzheimer-s-dementia
#13
Mandy Busse, Vanessa Hettler, Victoria Fischer, Christian Mawrin, Roland Hartig, Henrik Dobrowolny, Bernhard Bogerts, Thomas Frodl, Stefan Busse
The role of monocytes and macrophages in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD) is poorly understood. Recently, we have shown that the number of CD14+ monocytes remained constant during healthy aging and in AD patients. Although only little is known about the function of activated macrophages and microglia in AD, one important mechanism involves the expression of quinolinic acid (QUIN), an endogenous N-methyl-D-aspartate glutamate receptor (NMDA-R) agonist which mediates excitotoxicity especially in the hippocampus...
April 6, 2017: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/28386671/alzheimer-s-senile-plaque-as-shown-by-microcryodissection-a-new-technique-for-dissociating-tissue-structures
#14
Manon Thierry, Serge Marty, Susana Boluda, Charles Duyckaerts
Extracellular accumulation of Aβ peptides and intracellular aggregation of hyperphosphorylated tau proteins are the two hallmark lesions of Alzheimer disease (AD). The senile plaque is made of a core of extracellular Aβ surrounded by phospho-tau positive neurites. It includes multiple components such as axons, synapses, glial fibers and microglia. To visualize the relationships of those elements, an original technique was developed, based on the dilation of interstitial water during freezing. Samples of neocortex, hippocampus and striatum were taken from formalin-fixed brains (one control case; three cases with severe Alzheimer disease)...
April 6, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28381303/retention-of-normal-glia-function-by-an-isoform-selective-protein-kinase-inhibitor-drug-candidate-that-modulates-cytokine-production-and-cognitive-outcomes
#15
Zhengqiu Zhou, Adam D Bachstetter, Claudia B Späni, Saktimayee M Roy, D Martin Watterson, Linda J Van Eldik
BACKGROUND: Brain p38α mitogen-activated protein kinase (MAPK), a potential therapeutic target for cognitive dysfunction based on the neuroinflammation-synaptic dysfunction cycle of pathophysiology progression, offers an innovative pharmacological strategy via inhibiting the same activated target in both glia and neurons, thereby enhancing the possibility for efficacy. The highly selective, brain-penetrant p38αMAPK inhibitor MW150 attenuates cognitive dysfunction in two distinct Alzheimer's disease (AD)-relevant models and avoids the problems encountered with previous mixed-kinase inhibitor drug candidates...
April 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28376694/identification-of-a-rare-coding-variant-in-trem2-in-a-chinese-individual-with-alzheimer-s-disease
#16
Luke W Bonham, Daniel W Sirkis, Jia Fan, Renan E Aparicio, Marian Tse, Eliana Marisa Ramos, Qing Wang, Giovanni Coppola, Howard J Rosen, Bruce L Miller, Jennifer S Yokoyama
Rare variation in the TREM2 gene is associated with a broad spectrum of neurodegenerative disorders including Alzheimer's disease (AD). TREM2 encodes a receptor expressed in microglia which is thought to influence neurodegeneration by sensing damage signals and regulating neuroinflammation. Many of the variants reported to be associated with AD, including the rare R47H variant, were discovered in populations of European ancestry and have not replicated in diverse populations from other genetic backgrounds. We utilized a cohort of elderly Chinese individuals diagnosed as cognitively normal, or with mild cognitive impairment or AD to identify a rare variant, A192T, present in a single patient diagnosed with AD...
February 2017: Neurocase
https://www.readbyqxmd.com/read/28373057/lysophosphatidylcholine-export-by-human-abca7
#17
Maiko Tomioka, Yoshinobu Toda, Noralyn B Mañucat, Hiroyasu Akatsu, Manabu Fukumoto, Nozomu Kono, Hiroyuki Arai, Noriyuki Kioka, Kazumitsu Ueda
The ATP-binding cassette transporter A7 (ABCA7), which is highly expressed in the brain, is associated with the pathogenesis of Alzheimer's disease (AD). However, the physiological function of ABCA7 and its transport substrates remain unclear. Immunohistochemical analyses of human brain sections from AD and non-AD subjects revealed that ABCA7 is expressed in neuron and microglia cells in the cerebral cortex. The transport substrates and acceptors were identified in BHK/ABCA7 cells and compared with those of ABCA1...
March 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28372329/dynamics-of-the-complement-cytokine-and-chemokine-systems-in-the-regulation-of-synaptic-function-and-dysfunction-relevant-to-alzheimer-s-disease
#18
Shanya Jiang, Kiran Bhaskar
Alzheimer's disease (AD) is the most common form of dementia affecting nearly 45 million people worldwide. However, the etiology of AD is still unclear. Accumulations of amyloid-β plaques and tau tangles, neuroinflammation, and synaptic and neuronal loss are the major neuropathological hallmarks of AD, with synaptic loss being the strongest correlating factor with memory and cognitive impairment in AD. Many of these pathological hallmarks influence each other during the onset and progression of the disease...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28365005/neocortical-and-hippocampal-trem2-protein-levels-during-the-progression-of-alzheimer-s-disease
#19
Sylvia E Perez, Muhammad Nadeem, Bin He, Jennifer C Miguel, Michael H Malek-Ahmadi, Kewei Chen, Elliott J Mufson
Heterozygous triggering receptor expressed on myeloid cells (TREM2) mutations are an Alzheimer's disease (AD) risk factor. Nonmutated TREM2 dysregulation occurs in AD brain. Whether TREM2 is altered in prodromal AD remains unknown. Western blotting was used to determine levels of TREM2 (∼25 kDa) and Iba1 in the frontal cortex and TREM2 in the hippocampus from people who died with an ante-mortem clinical diagnosis of non- and mild-cognitive impairment, mild/moderate AD, and severe AD (sAD). Immunohistochemistry defined the relationship between amyloid and Iba1 profiles...
June 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28346104/bioengineered-3d-glial-cell-culture-systems-and-applications-for-neurodegeneration-and-neuroinflammation
#20
P Marc D Watson, Edel Kavanagh, Gary Allenby, Matthew Vassey
Neurodegeneration and neuroinflammation are key features in a range of chronic central nervous system (CNS) diseases such as Alzheimer's and Parkinson's disease, as well as acute conditions like stroke and traumatic brain injury, for which there remains significant unmet clinical need. It is now well recognized that current cell culture methodologies are limited in their ability to recapitulate the cellular environment that is present in vivo, and there is a growing body of evidence to show that three-dimensional (3D) culture systems represent a more physiologically accurate model than traditional two-dimensional (2D) cultures...
February 1, 2017: SLAS Discovery
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