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Amyloid aging microglia

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https://www.readbyqxmd.com/read/28611242/evaluation-of-%C3%AE-pet-outcome-measures-to-detect-disease-modification-induced-by-bace-inhibition-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#1
Steven Deleye, Ann Marie Waldron, Jeroen Verhaeghe, Astrid Bottelbergs, Leonie Wyffels, Bianca Van Broeck, Xavier Langlois, Mark E Schmidt, Sigrid Stroobants, Steven Staelens
Purpose: In this study, we investigated the effects of chronic administration of an inhibitor of the β-site amyloid precursor protein -cleaving enzyme 1 (BACE1) on Alzheimer's- related pathology by multi-tracer positron emission tomography (PET) imaging in APPPS1-21 mice. Methods: Wild-type (WT) and APPPS1-21 (TG) mice received vehicle (VEH) or BACE inhibitor (60 mg/kg) initiated at 7 weeks of age. Outcome measures of brain metabolism, neuroinflammation and amyloid-β pathology were obtained through μPET imaging with (18)F-FDG, (18)F-PBR111 and (18)F-AV45 respectively...
June 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28610747/cathepsin-b-plays-a-critical-role-in-inducing-alzheimer-s-disease-like-phenotypes-following-chronic-systemic-exposure-to-lipopolysaccharide-from-porphyromonas-gingivalis-in-mice
#2
Zhou Wu, Junjun Ni, Yicong Liu, Jessica L Teeling, Fumiko Takayama, Alex Collcutt, Paul Ibbett, Hiroshi Nakanishi
A number of clinical and experimental studies have revealed a strong association between periodontitis and accelerated cognitive decline in Alzheimer's disease (AD); however, the mechanism of the association is unknown. In the present study, we tested the hypothesis that cathepsin (Cat) B plays a critical role in the initiation of neuroinflammation and neural dysfunction following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis (PgLPS) in mice (1mg/kg, daily, intraperitoneally)...
June 10, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28579942/voluntary-exercise-promotes-glymphatic-clearance-of-amyloid-beta-and-reduces-the-activation-of-astrocytes-and-microglia-in-aged-mice
#3
Xiao-Fei He, Dong-Xu Liu, Qun Zhang, Feng-Ying Liang, Guang-Yan Dai, Jin-Sheng Zeng, Zhong Pei, Guang-Qing Xu, Yue Lan
Age is characterized by chronic inflammation, leading to synaptic dysfunction and dementia because the clearance of protein waste is reduced. The clearance of proteins depends partly on the permeation of the blood-brain barrier (BBB) or on the exchange of water and soluble contents between the cerebrospinal fluid (CSF) and the interstitial fluid (ISF). A wealth of evidence indicates that physical exercise improves memory and cognition in neurodegenerative diseases during aging, such as Alzheimer's disease (AD), but the influence of physical training on glymphatic clearance, BBB permeability and neuroinflammation remains unclear...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28566429/complement-c3-deficiency-protects-against-neurodegeneration-in-aged-plaque-rich-app-ps1-mice
#4
Qiaoqiao Shi, Saba Chowdhury, Rong Ma, Kevin X Le, Soyon Hong, Barbara J Caldarone, Beth Stevens, Cynthia A Lemere
The complement cascade not only is an innate immune response that enables removal of pathogens but also plays an important role in microglia-mediated synaptic refinement during brain development. Complement C3 is elevated in Alzheimer's disease (AD), colocalizing with neuritic plaques, and appears to contribute to clearance of Aβ by microglia in the brain. Previously, we reported that C3-deficient C57BL/6 mice were protected against age-related and region-specific loss of hippocampal synapses and cognitive decline during normal aging...
May 31, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28477083/peritoneal-dialysis-reduces-amyloid-beta-plasma-levels-in-humans-and-attenuates-alzheimer-associated-phenotypes-in-an-app-ps1-mouse-model
#5
Wang-Sheng Jin, Lin-Lin Shen, Xian-Le Bu, Wei-Wei Zhang, Si-Han Chen, Zhi-Lin Huang, Jia-Xiang Xiong, Chang-Yue Gao, Zhifang Dong, Ya-Ni He, Zhi-An Hu, Hua-Dong Zhou, Weihong Song, Xin-Fu Zhou, Yi-Zheng Wang, Yan-Jiang Wang
Clearance of amyloid-beta (Aβ) from the brain is an important therapeutic strategy for Alzheimer's disease (AD). Current studies mainly focus on the central approach of Aβ clearance by introducing therapeutic agents into the brain. In a previous study, we found that peripheral tissues and organs play important roles in clearing brain-derived Aβ, suggesting that the peripheral approach of removing Aβ from the blood may also be effective for AD therapy. Here, we investigated whether peritoneal dialysis, a clinically available therapeutic method for chronic kidney disease (CKD), reduces brain Aβ burden and attenuates AD-type pathologies and cognitive impairments...
May 5, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28442216/trem2-microglia-and-neurodegenerative-diseases
#6
REVIEW
Felix L Yeh, David V Hansen, Morgan Sheng
Alzheimer's disease (AD) is the most common form of dementia and the 6th leading cause of death in the US. The neuropathological hallmarks of the disease are extracellular amyloid-β (Aβ) plaques and intraneuronal hyperphosphorylated tau aggregates. Genetic variants of TREM2 (triggering receptor expressed on myeloid cells 2), a cell-surface receptor expressed selectively in myeloid cells, greatly increase the risk of AD, implicating microglia and the innate immune system as pivotal factors in AD pathogenesis...
April 22, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28427563/neuroinflammation-in-alzheimer-s-disease-the-preventive-and-therapeutic-potential-of-polyphenolic-nutraceuticals
#7
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/28282924/autophagy-and-microglia-novel-partners-in-neurodegeneration-and-aging
#8
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/28253987/metabolic-syndrome-and-the-cellular-phase-of-alzheimer-s-disease
#9
S Pugazhenthi
Alzheimer's disease (AD) is characterized by cognitive dysfunction and progressive neurodegeneration. The major hallmarks of AD pathology are amyloid plaques and neurofibrillary tangles. However, AD often coexists with other brain microvascular lesions caused by comorbidities, including obesity, diabetes, hypertension, and cardiovascular diseases. The risk factors for these comorbidities are collectively referred to as metabolic syndrome (MetS). Clinical AD is preceded by decades of prodromal cellular phase...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28203202/plasma-exosomes-spread-and-cluster-around-%C3%AE-amyloid-plaques-in-an-animal-model-of-alzheimer-s-disease
#10
Tingting Zheng, Jiali Pu, Yanxing Chen, Yanfang Mao, Zhangyu Guo, Hongyu Pan, Ling Zhang, Heng Zhang, Binggui Sun, Baorong Zhang
Exosomes, a type of extracellular vesicle, have been shown to be involved in many disorders, including Alzheimer's disease (AD). Exosomes may contribute to the spread of misfolded proteins such as amyloid-β (Aβ) and α-synuclein. However, the specific diffusion process of exosomes and their final destination in brain are still unclear. In the present study, we isolated exosomes from peripheral plasma and injected them into the hippocampus of an AD mouse model, and investigated exosome diffusion. We found that injected exosomes can spread from the dentate gyrus (DG) to other regions of hippocampus and to the cortex...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28197095/increase-of-trem2-during-aging-of-an-alzheimer-s-disease-mouse-model-is-paralleled-by-microglial-activation-and-amyloidosis
#11
Matthias Brendel, Gernot Kleinberger, Federico Probst, Anna Jaworska, Felix Overhoff, Tanja Blume, Nathalie L Albert, Janette Carlsen, Simon Lindner, Franz Josef Gildehaus, Laurence Ozmen, Marc Suárez-Calvet, Peter Bartenstein, Karlheinz Baumann, Michael Ewers, Jochen Herms, Christian Haass, Axel Rominger
Heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been reported to significantly increase the risk of developing Alzheimer's disease (AD). Since TREM2 is specifically expressed by microglia in the brain, we hypothesized that soluble TREM2 (sTREM2) levels may increase together with in vivo biomarkers of microglial activity and amyloidosis in an AD mouse model as assessed by small animal positron-emission-tomography (μPET). In this cross-sectional study, we examined a strong amyloid mouse model (PS2APP) of four age groups by μPET with [(18)F]-GE180 (glial activation) and [(18)F]-florbetaben (amyloidosis), followed by measurement of sTREM2 levels and amyloid levels in the brain...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28185874/psychosocial-stress-on-neuroinflammation-and-cognitive-dysfunctions-in-alzheimer-s-disease-the-emerging-role-for-microglia
#12
REVIEW
Sami Piirainen, Andrew Youssef, Cai Song, Allan V Kalueff, Gary E Landreth, Tarja Malm, Li Tian
Chronic psychosocial stress is increasingly recognized as a risk factor for late-onset Alzheimer's disease (LOAD) and associated cognitive deficits. Chronic stress also primes microglia and induces inflammatory responses in the adult brain, thereby compromising synapse-supportive roles of microglia and deteriorating cognitive functions during aging. Substantial evidence demonstrates that failure of microglia to clear abnormally accumulating amyloid-beta (Aβ) peptide contributes to neuroinflammation and neurodegeneration in AD...
June 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28143566/apoe-genotype-differentially-modulates-effects-of-anti-a%C3%AE-passive-immunization-in-app-transgenic-mice
#13
Joanna E Pankiewicz, Jairo Baquero-Buitrago, Sandrine Sanchez, Jennifer Lopez-Contreras, Jungsu Kim, Patrick M Sullivan, David M Holtzman, Martin J Sadowski
BACKGROUND: APOE genotype is the foremost genetic factor modulating β-amyloid (Aβ) deposition and risk of sporadic Alzheimer's disease (AD). Here we investigated how APOE genotype influences response to anti-Aβ immunotherapy. METHODS: APPSW/PS1dE9 (APP) transgenic mice with targeted replacement of the murine Apoe gene for human APOE alleles received 10D5 anti-Aβ or TY11-15 isotype control antibodies between the ages of 12 and 15 months. RESULTS: Anti-Aβ immunization decreased both the load of fibrillar plaques and the load of Aβ immunopositive plaques in mice of all APOE backgrounds...
January 31, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28123027/innate-immunity-stimulation-via-toll-like-receptor-9-ameliorates-vascular-amyloid-pathology-in-tg-swdi-mice-with-associated-cognitive-benefits
#14
Henrieta Scholtzova, Eileen Do, Shleshma Dhakal, Yanjie Sun, Shan Liu, Pankaj D Mehta, Thomas Wisniewski
Alzheimer's disease (AD) is characterized by the presence of parenchymal amyloid-β (Aβ) plaques, cerebral amyloid angiopathy (CAA) and neurofibrillary tangles. Currently there are no effective treatments for AD. Immunotherapeutic approaches under development are hampered by complications related to ineffectual clearance of CAA. Genome-wide association studies have demonstrated the importance of microglia in AD pathogenesis. Microglia are the primary innate immune cells of the brain. Depending on their activation state and environment, microglia can be beneficial or detrimental...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28122877/an-early-and-late-peak-in-microglial-activation-in-alzheimer-s-disease-trajectory
#15
Zhen Fan, David J Brooks, Aren Okello, Paul Edison
Amyloid-β deposition, neuroinflammation and tau tangle formation all play a significant role in Alzheimer's disease. We hypothesized that there is microglial activation early on in Alzheimer's disease trajectory, where in the initial phase, microglia may be trying to repair the damage, while later on in the disease these microglia could be ineffective and produce proinflammatory cytokines leading to progressive neuronal damage. In this longitudinal study, we have evaluated the temporal profile of microglial activation and its relationship between fibrillar amyloid load at baseline and follow-up in subjects with mild cognitive impairment, and this was compared with subjects with Alzheimer's disease...
March 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28087694/iso-%C3%AE-acids-bitter-components-of-beer-prevent-inflammation-and-cognitive-decline-induced-in-a-mouse-model-of-alzheimer-s-disease
#16
Yasuhisa Ano, Atsushi Dohata, Yoshimasa Taniguchi, Ayaka Hoshi, Kazuyuki Uchida, Akihiko Takashima, Hiroyuki Nakayama
Alongside the rapid growth in aging populations worldwide, prevention and therapy for age-related memory decline and dementia are in great demand to maintain a long, healthy life. Here we found that iso-α-acids, hop-derived bitter compounds in beer, enhance microglial phagocytosis and suppress inflammation via activation of the peroxisome proliferator-activated receptor γ. In normal mice, oral administration of iso-α-acids led to a significant increase both in CD11b and CD206 double-positive anti-inflammatory type microglia (p < 0...
March 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28073379/tau-passive-immunization-inhibits-not-only-tau-but-also-a%C3%AE-pathology
#17
Chun-Ling Dai, Yunn Chyn Tung, Fei Liu, Cheng-Xin Gong, Khalid Iqbal
BACKGROUND: Accumulation of hyperphosphorylated tau protein is a histopathological hallmark of Alzheimer's disease (AD) and related tauopathies. Currently, there is no effective treatment available for these progressive neurodegenerative diseases. In recent years, tau immunotherapy has shown great potential in animal models. We report the effect of immunization with tau antibodies 43D against tau 6-18 and 77E9 against tau 184-195 on tau and amyloid-β (Aβ) pathologies and cognition in triple-transgenic (3×Tg)-AD mice at mild to moderate stages of the disease...
January 10, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28060896/isobavachalcone-attenuates-mptp-induced-parkinson-s-disease-in-mice-by-inhibition-of-microglial-activation-through-nf-%C3%AE%C2%BAb-pathway
#18
Haoran Jing, Shaoxia Wang, Min Wang, Wenliang Fu, Chao Zhang, Donggang Xu
Parkinson's disease (PD) is a complex multi-system and age-related neurodegenerative disorder. The intervention targeting neuroinflammation in PD patients is one effective strategy to slow down or inhibit disease progression. Microglia-mediated inflammatory response plays an important role in Parkinson's, Alzheimer's and other cerebral diseases. Isobavachalcone is a main component of Chinese herb medicine Psoralea corylifolia, which function includes immunoregulation, anti-oxidation and the regulation of β-amyloid (Aβ42) deposited in hippocampus in Alzheimer's patients...
2017: PloS One
https://www.readbyqxmd.com/read/28054940/neuroprotective-effects-of-aged-garlic-extract-on-cognitive-dysfunction-and-neuroinflammation-induced-by-%C3%AE-amyloid-in-rats
#19
Nutchareeporn Nillert, Wanassanun Pannangrong, Jariya Umka Welbat, Wunnee Chaijaroonkhanarak, Kittisak Sripanidkulchai, Bungorn Sripanidkulchai
Neuroinflammation is pathological evidence of Alzheimer's disease (AD) that likely starts as a host defense response to the damaging effects of the β-amyloid (Aβ) deposits in the brain. The activation of microglia may promote the neurodegenerative process through the release of proinflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), which may lead to neuronal damage and eventual death. Aged garlic extract (AGE) has been reported to have multiple biological activities, including anti-inflammatory effects...
January 3, 2017: Nutrients
https://www.readbyqxmd.com/read/28039950/ageing-causes-prominent-neurovascular-dysfunction-associated-with-loss-of-astrocytic-contacts-and-gliosis
#20
J Duncombe, R J Lennen, M A Jansen, I Marshall, J M Wardlaw, K Horsburgh
AIMS: Normal neurovascular coupling, mediated by the fine interplay and communication of cells within the neurovascular unit, is critical for maintaining normal brain activity and cognitive function. This study investigated whether, with advancing age there is disruption of neurovascular coupling and specific cellular components of the neurovascular unit, and whether the effects of increasing amyloid (a key feature of Alzheimer's disease) would exacerbate these changes. METHODS: Wild-type mice, in which amyloid deposition is absent, were compared to transgenic amyloid precursor protein (APP) littermates (TgSwDI) which develop age-dependent increases in amyloid...
December 31, 2016: Neuropathology and Applied Neurobiology
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