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Functional Impairment of Microglia Coincides with Beta-Amyloid Deposition in Mice with Alzheimer-Like Pathology
Open accessAbstract
Microglial cells closely interact with senile plaques in Alzheimer's disease and acquire the morphological appearance of an activated phenotype. The significance of this microglial phenotype and the impact of microglia for disease progression have remained controversial. To uncover and characterize putative changes in the functionality of microglia during Alzheimer's disease, we directly assessed microglial behavior in two mouse models of Alzheimer's disease. Using in vivo two-photon microscopy and acute brain slice preparations, we found that important microglial functions - directed process motility and phagocytic activity - were strongly impaired in mice with Alzheimer's disease-like pathology compared to age-matched non-transgenic animals. Notably, impairment of microglial function temporally and spatially correlated with Aβ plaque deposition, and phagocytic capacity of microglia could be restored by interventionally decreasing amyloid burden by Aβ vaccination. These data suggest that major microglial functions progressively decline in Alzheimer's disease with the appearance of Aβ plaques, and that this functional impairment is reversible by lowering Aβ burden, e.g. by means of Aβ vaccination.
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“Notably, previous studies have shown that microglial function may be adversely affected by Aβ, particularly as a result of chronic exposure to pro-inflammatory cytokines, resulting in increased Aβ accumulation and potentially underpinning the contradiction between our in vitro and in vivo results.39,40”
From Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [39]
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“the ability of microglia to remove Αβ declines over time”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [17]
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“supporting that the progression of amyloid pathology correlates with impaired capacity of microglia to phagocytose Αβ17,16.”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [17]
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“their phagocytic capacity declines with aging, chronic exposure to Αβ, and during sustained inflammation in the AD brain76,16,17.”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [17]
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“However, perturbations in microglial activity, often associated with aging, can affect the effective clearance of these neuron-derived Aβ fibrils, leading to increased plaque formation and the progression of cognitive and behavioral impairments (17–20).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [19]
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“Microglial phagocytosis is believed to be dysfunctional in AD [17–19].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [18]
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“However, several studies have shown that defects in the phagocytic function of microglia can be restored with Aβ immunization [18, 23] and anti-inflammatory drug treatment [24, 25].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [18]
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“Notably, microglial process motility directed toward site of damage was significantly impaired in mice with A β plaques 48 .”
From Transcriptomic analysis of purified human cortical microglia reveals age-associated changes (2017) · cites this paper as [48]
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Citations
Cites
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Items 201–300 of 483
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Hierro‐Bujalance, C., Bacskai, B. J., & García-Alloza, M. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00218 · Cited by 50
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Glial Purinergic Signaling in Neurodegeneration
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“Another important microglial cell function that is affected in neurodegeneration is the phagocytic capacity (87), which among many other mechanisms, is regulated by the UDP-sensitive”
BackgroundSelf-citationImmunity and Alzheimer's disease: immunological perspectives on the development of novel therapies
Liu, Y.-H., Zeng, F., Wang, Y., Zhou, H., Giunta, B. N., Tan, J., & Wang, Y. (2013) · Drug Discovery Today · doi:10.1016/j.drudis.2013.07.020 · Cited by 48
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Immune-mediated processes in neurodegeneration: where do we stand?
Fakhoury, M. (2016) · Journal of Neurology · doi:10.1007/s00415-016-8052-0 · Cited by 43
“progression of AD, and is associated with the appearance of Ab plaques in the brain [117].”
BackgroundCERTL reduces C16 ceramide, amyloid-β levels, and inflammation in a model of Alzheimer’s disease
Crivelli, S. M., Luo, Q., Stevens, J., Giovagnoni, C., van Kruining, D., Bode, G. H., den Hoedt, S., Hobo, B., Scheithauer, A.-L., Walter, J., et al. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-021-00780-0 · Cited by 41
“Elucidation of the dysregulated biological mechanisms that lead to the onset and progression of AD is critical to identify new treatment strategies (1-5).”
BackgroundMotiQ: an open-source toolbox to quantify the cell motility and morphology of microglia
Hansen, J. N., Brückner, M., Pietrowski, M. J., Jikeli, J. F., Plescher, M., Beckert, H., Schnaars, M., Fülle, L., Reitmeier, K., Langmann, T., et al. (2022) · Molecular Biology of the Cell · doi:10.1091/mbc.e21-11-0585 · Cited by 44
“Primary microglia Primary mixed glial cultures were generated to obtain cultured microglia as described (Krabbe et al., 2013).”
BackgroundMethodSelf-citationNeuroinflammation in Alzheimer's disease and beneficial action of luteolin
Delgado, A., Cholevas, C., & Theoharides, T. C. (2021) · BioFactors · doi:10.1002/biof.1714 · Cited by 48
“Yet, the cell's prolonged activity eventually renders them capable of contributing to an environment of neurotoxicity through sustained release of proinflammatory cytokines and chemokines, toxic free radicals and the initiation of the complement cascade.(67,68) Moreover, microglia can contribute to the spread of NFTs…”
BackgroundSinha, A., Kushwaha, R., Molesworth, K., Mychko, O., Makarava, N., & Baskakov, I. V. (2021) · Cells · doi:10.3390/cells10071728 · Cited by 42
Dissecting Alzheimer disease in Down syndrome using mouse models
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“Both LPS and Aβ peptides induce microglia activation which leads to the release of pro-inflammatory mediators such as IL-6, TNF-α, and NO (Mandrekar and Landreth 2010; Krabbe et al. 2013; Cai et al. 2014; Fan et al. 2015).”
BackgroundNLRP3 and Infections: β-Amyloid in Inflammasome beyond Neurodegeneration
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Presenilin 1 phosphorylation regulates amyloid-β degradation by microglia
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“In addition, the impairment of directed motility was associated with decreased phagocytic activity and was observed together with morphological changes in plaque-associated cells in AD mouse models [21].”
BackgroundHeme and hemoglobin suppress amyloid β–mediated inflammatory activation of mouse astrocytes
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Molecular Bases of Alzheimer’s Disease and Neurodegeneration: The Role of Neuroglia
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“In addition, AD is characterized by an unbalance between inflammatory and clearing properties of microglia [189] and it has been proposed that lowering the Aβ burden would restore an efficient microglial functioning [191].”
BackgroundThe Role of Sphingolipids and Specialized Pro-Resolving Mediators in Alzheimer’s Disease
de Wit, N. M., Mol, K., Rodríguez‐Lorenzo, S., de Vries, H. E., & Kooij, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.620348 · Cited by 40
“Additionally, microglia surrounding senile plaque become impaired in Ab uptake and clearance, causing further accumulation of Ab thereby inducing a prolonged inflammatory response with continuous secretion of proinflammatory mediators (41).”
BackgroundChen, Y., Hong, T., Chen, F., Sun, Y., Wang, Y., & Cui, L. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.631827 · Cited by 40
Synapse development is regulated by microglial THIK-1 K + channels
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“Following a recovery period of a few hours after brain slicing, which allows some microglial activation to occur (29), fluorophore-labeled resin microbeads were applied (30, 31) onto rat hippocampal slices in the presence or absence of pharmacological blockers (Fig.”
MethodAmyloid β Induces Lipid Droplet‐Mediated Microglial Dysfunction in Alzheimer’s Disease
Prakash, P., Manchanda, P., Paouri, E., Bisht, K., Sharma, K. P., Rajpoot, J., Wendt, V., Hossain, A., Wijewardhane, P. R., Randolph, C. E., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.075938 · Cited by 38
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miR-146a Dysregulates Energy Metabolism During Neuroinflammation
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“Reduced Aβ uptake capacity of microglia in the brain has been suggested as a major cause for AD (Lee and Landreth, 2010; Krabbe et al., 2013).”
BackgroundVargas-Restrepo, F., Sabogal-Guáqueta, A. M., & Cardona‐Gómez, G. P. (2017) · Biomédica · doi:10.7705/biomedica.v38i0.3761 · Cited by 36
“This suggests that the induction of βA phagocytosis (4,36) and the decrease in the release of neurotoxic cytokines (2) are mediating the protective action of quercetin, because in our previous observations quercetin did not regulate typical tauopathy mediator enzymes, such as CDK5 and GSK3-beta (17).”
BackgroundMicroglia in Alzheimer's Disease: A Role for Ion Channels
Thei, L., Imm, J. L., Kaisis, E., Dallas, M. L., & Kerrigan, T. L. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00676 · Cited by 37
Microglia and modifiable life factors: Potential contributions to cognitive resilience in aging
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New insights in drug development for Alzheimer's disease based on microglia function
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Animal models in the study of Alzheimer's disease and Parkinson's disease: A historical perspective
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“Microglial morphology is believed to be tightly linked to its function [60, 135].”
Haw, R. T. Y., Tong, C. K., Yew, A., Lee, H. C., Phillips, J. B., & Vidyadaran, S. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-134 · Cited by 33
“Brain slice culture allows in situ examination of cellular responses, and has been used to study microglial responses to carcinomas [10] and cerebral amyloidosis [11].”
BackgroundJhang, K. A., Park, J., Kim, H.-S., & Chong, Y. H. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1112-x · Cited by 32
“In addition, the presence of amyloid acts to suppress macrophage phagocytic function [32].”
Endocannabinoid signalling in Alzheimer's disease
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“As microglia function declines in aged AD mice (Krabbe et al., 2013), the treatment targeting microglia in AD should attempt to switch microglial phenotypes from the disease state to the healthy state (Wes et al.”
Zuroff, L. R., Torbati, T., Hart, N. J., Fuchs, D.-T. S., Sheyn, J., Rentsendorj, A., Koronyo, Y., Hayden, E. Y., Teplow, D. B., Black, K. L., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01449 · Cited by 29
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The Pathological Activation of Microglia Is Modulated by Sexually Dimorphic Pathways
O'Connor, J. L., & Nissen, J. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054739 · Cited by 33
Neutrophil to lymphocyte ratio in Alzheimer’s disease: A systematic review and meta-analysis
Mohammadi, A., Mohammadi, M., Almasi‐Dooghaee, M., & Mirmosayyeb, O. (2024) · PLoS ONE · doi:10.1371/journal.pone.0305322 · Cited by 30
“As inflammation continues, it triggers the release of more inflammatory cytokines while simultaneously boosting the number of macrophages to address and combat the accumulation of plaque [38, 39].”
BackgroundGuo, X., Tang, P., Chen, L., Liu, P., Hou, C., Zhang, X., Liu, Y., Li, C., Li, X., & Li, R. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00228 · Cited by 34
“Studies have shown that the function of lysosomal enzymes in the microglia of AD patients was potentially impaired, leading to the dysfunction in clearing misfolded Aβ and autophagy impairment (Krabbe et al., 2013), however, the underlying mechanism remained unknown (Majumdar et al., 2007).”
BackgroundLosartan Improves Memory, Neurogenesis and Cell Motility in Transgenic Alzheimer’s Mice
Drews, H. J., Klein, R., Lourhmati, A., Buadze, M., Schaeffeler, E., Lang, T., Seferyan, T., Hanson, L. R., Frey, W. H., de Vries, T. C. G. M., et al. (2021) · Pharmaceuticals · doi:10.3390/ph14020166 · Cited by 32
“The decrease in anti-inflammatory cytokines shown here led us to test whether these losartan-evoked changes can affect the motility and phagocytotic function of microglia, which are both impaired in mice with AD-like pathology [24].”
BackgroundAlzheimer's disease and synapse Loss: What can we learn from induced pluripotent stem Cells?
Rodríguez-Jiménez, F. J., Ureña‐Peralta, J. R., Jendelová, P., & Erceg, S. (2023) · Journal of Advanced Research · doi:10.1016/j.jare.2023.01.006 · Cited by 33
“As plaque load increases in AD, an individual axon may suffer multiple points of damage, and microglia appear unable to clear the amyloid burden during later-stage AD [168].”
BackgroundInnate immunity in Alzheimer’s disease: the relevance of animal models?
Franco-Bocanegra, D., Nicoll, J. A. R., & Boche, D. (2017) · Journal of Neural Transmission · doi:10.1007/s00702-017-1729-4 · Cited by 32
“These results are relevant in the light of the findings discussed in the previous section regarding microglial motility and phagocytic activity, that microglial motility in AD transgenic mice is decreased and this impairment is spatially correlated with the presence of amyloid plaques (Krabbe et al. 2013).”
BackgroundResultInfluentialHayek, D., Ziegler, G., Kleineidam, L., Brosseron, F., Nemali, A., Vockert, N., Ravichandran, K. A., Betts, M. J., Peters, O., Schneider, L., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-023-02387-3 · Cited by 32
“However, if release of proin fl ammatory mediators is sustained, chronic in fl ammation might contribute to neurodegeneration and white matter (WM) injury [5].”
BackgroundStratoulias, V., & Heino, T. I. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1789-7 · Cited by 29
“For instance, the phagocytic function of microglia is impaired in mice with Alzheimer-like pathology [23, 26], as well as in prion diseased brains [44, 53].”
BackgroundLiu, Y.-H., Jiao, S.-S., Wang, Y.-R., Bu, X.-L., Yao, X., Xiang, Y., Wang, Q.-H., Wang, L., Deng, J., Li, J., et al. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8804-8 · Cited by 30
Richter, M., Vidovic, N., Biber, K. P. H., Dolga, A. M., Culmsee, C., & Dodel, R. C. (2019) · Brain Pathology · doi:10.1111/bpa.12807 · Cited by 31
“We thus confirmed and elaborated recent findings that microglia in OHSCs take up Aβ (33, 91), which corroborates in vivo studies demonstrating that microglia from wild-type mice efficiently engulf Aβ (53, 83).”
ResultChen, Z., Maqbool, J., Sajid, F., Hussain, G., & Sun, T. (2020) · Microbial Pathogenesis · doi:10.1016/j.micpath.2020.104675 · Cited by 28
Pharmacological considerations for treating neuroinflammation with curcumin in Alzheimer’s disease
Zhou, X., Venigalla, M., Raju, R., & Münch, G. W. (2022) · Journal of Neural Transmission · doi:10.1007/s00702-022-02480-x · Cited by 34
“As a characteristic example, APPPS1 mice (a transgenic mouse model of cerebral amyloidosis expressing human amyloid precursor protein (APP) with the Swedish mutation (KM670/671NL) and human mutated presenilin-1 (PS1)-L166P)) exhibit two very distinct morphological microglial phenotypes: cells close to the plaques exhi…”
BackgroundWątroba, M., & Szukiewicz, D. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.962769 · Cited by 29
“Phagocytic efficacy of microglial cells can be restored by reducing Aβ burden (Krabbe et al., 2013).”
BackgroundLessons Learned about Neurodegeneration from Microglia and Monocyte Depletion Studies
Lund, H., Pieber, M., & Harris, R. A. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00234 · Cited by 27
“This is supported by evidence that microglia in the vicinity of amyloid beta plaques progressively lose phagocytic capacity (Hickman et al., 2008; Krabbe et al., 2013).”
BackgroundPeng, L., Parpura, V., & Verkhratsky, A. (2014) · Current Neuropharmacology · doi:10.2174/1570159x12999140829152550 · Cited by 29
“Reactive astrogliosis and activation of microglia usually appear in response to disease-specific lesions.”
Song, H., Liu, J., Wang, L., Hu, X., Li, J., Zhu, L., Pang, R., & Zhang, A. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1348844 · Cited by 26
The complex effects of miR-146a in the pathogenesis of Alzheimer’s disease
Long, Y., Liu, J., Wang, Y., Guo, H.-D., & Cui, G.-H. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01566 · Cited by 34
Sleep–Wake Disorders in Alzheimer’s Disease: A Review
Sun, Y.-Y., Wang, Z., Zhou, H.-Y., & Huang, H. (2022) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.2c00097 · Cited by 27
Heart and Brain: Complex Relationships for Left Ventricular Dysfunction
Daniele, G., DiLucia, S., Masci, P. G., & del Monte, F. (2020) · Current Cardiology Reports · doi:10.1007/s11886-020-01318-w · Cited by 27
Microglia as a cellular target of diclofenac therapy in Alzheimer’s disease
Stopschinski, B. E., Weideman, R. A., McMahan, D., Jacob, D. A., Little, B. B., Chiang, H.-S., Saez Calveras, N., & Stuve, O. (2023) · Therapeutic Advances in Neurological Disorders · doi:10.1177/17562864231156674 · Cited by 26
Myelin, aging, and physical exercise
Graciani, A. L., Gutierre, M. U., Ribeiro, A. A. C. M., Arida, R. M., & Gutierre, R. C. (2023) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2023.03.009 · Cited by 28
Lana, D., Traini, C., Bulli, I., Sarti, G., Magni, G., Attorre, S., Giovannini, M. G., & Vannucchi, M. G. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1451114 · Cited by 27
“However, in later stages of the disease microglia lose their ability to remove and destroy A β (Krabbe et al., 2013).”
BackgroundProMoIJ: A new tool for automatic three‐dimensional analysis of microglial process motility
Paris, I., Savage, J. C., Escobar, L., Abiega, O., Gagnon, S., Hui, C. W., Tremblay, M., Sierra, A., & Valero, J. (2017) · Glia · doi:10.1002/glia.23287 · Cited by 25
“…(Kondo, Kohsaka, & Okabe, 2011; Batti et al., 2016; Fourgeaud et al., 2016), volume/area occupied by microglial processes (Davalos et al., 2005; Krabbe et al., 2013; Batti et al., 2016; Sipe et al., 2016), microglial volume, area, perimeter, number of branches per cell, or cell mass center…”
BackgroundMethodInfluentialMicrofluidic Platforms to Unravel Mysteries of Alzheimer’s Disease: How Far Have We Come?
Prasanna, P., Rathee, S., Rahul, V., Mandal, D., Goud, M. S. C., Yadav, P., Hawthorne, S. J., Sharma, A., Gupta, P. K., Ojha, S. K., et al. (2021) · Life · doi:10.3390/life11101022 · Cited by 25
“Primary cultures have been extensively used to investigate the role of Aβ pathology both in astrocytes [72] and microglia [73].”
BackgroundGullo, F., Amadeo, A., Donvito, G., Lecchi, M., Costa, B., Constanti, A., & Wanke, E. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00361 · Cited by 26
“Also, microglial cells [the resident immune cells of the central nervous system (CNS)], play a critical role in neuropathology following brain injury (Perry et al., 2010; Krabbe et al., 2013).”
BackgroundInfluentialContributions of Microglia to Structural Synaptic Plasticity
Kim, K. H., Son, S. M., & Mook‐Jung, I. (2013) · Journal of Experimental Neuroscience · doi:10.4137/jen.s11269 · Cited by 25
Microglia in Alzheimer’s Disease
Süß, P., & Schlachetzki, J. C. M. (2020) · Current Alzheimer Research · doi:10.2174/1567205017666200212155234 · Cited by 26
Biological and therapeutic role of LSD1 in Alzheimer’s diseases
Li, Y., Zhao, Y., Li, X., Zhai, L., Zheng, H., Yan, Y., Fu, Q., Ma, J., Fu, H., Zhang, Z., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1020556 · Cited by 25
“Besides, accumulation of Aβ and neuronal debris could also activate inflammatory factors to stimulate chronic inflammation (Streit et al., 2009; Krabbe et al., 2013).”
BackgroundN-3 polyunsaturated fatty acid and neuroinflammation in aging and Alzheimer's disease
Layé, S., Madore, C., St‐Amour, I., Delpech, J.-C., Joffre, C., Nadjar, A., & Calon, F. (2015) · Nutrition and Aging · doi:10.3233/nua-150049 · Cited by 24
“Recent data highlighted that microglia, because of its impaired activity in the AD brain, cannot phagocytocize A that therefore accumulates [102, 103].”
Verkhratsky, A., Zorec, R., Rodriguez, J. J., & Parpura, V. (2017) · Advances in neurobiology · doi:10.1007/978-3-319-57193-5_17 · Cited by 23
NVP-BEZ235 (Dactolisib) Has Protective Effects in a Transgenic Mouse Model of Alzheimer’s Disease
Bellozi, P. M. Q., Gomes, G. F., de Oliveira, L. R., Olmo, I. G., Vieira, É. L. M., Ribeiro, F. M., Fiebich, B. L., & de Oliveira, A. C. P. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01345 · Cited by 22
Proteome analysis in the assessment of ageing
Nkuipou‐Kenfack, E., Koeck, T., Mischak, H., Pich, A., Schanstra, J. P., Zürbig, P., & Schumacher, B. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.09.002 · Cited by 22
Rollercoaster ride of kynurenines: steering the wheel towards neuroprotection in Alzheimer’s disease
Sharma, R., Razdan, K., Bansal, Y., & Kuhad, A. (2018) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2018.1524877 · Cited by 22
“tent functional impairment ofmicroglial cells seen at plaque sites [65,66].”
BackgroundThe Complementary Role of Morphology in Understanding Microglial Functional Heterogeneity
Godeanu, S., & Cătălin, B. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26083811 · Cited by 22
“Process or soma motility [24,90] Direction Process or soma motility 24,90] Direction Process or soma motility [24,90] Direction”
DiBona, V. L., Zhu, W., Shah, M. K., Rafalia, A., Cheikh, H. B., Crockett, D. P., & Zhang, H. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1390-3 · Cited by 21
“studies show that microglia process motility decreases in the aging brain [53–55] and is impaired in certain pathological conditions including Alzheimer’s disease [56, 57] and Huntington’s disease [58].”
BackgroundOligomeric Forms of Human Amyloid-Beta(1–42) Inhibit Antigen Presentation
Gericke, C., Mallone, A., Engelhardt, B., Nitsch, R. M., & Ferretti, M. T. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01029 · Cited by 20
“In addition to the wellstudied AD pathology-related alterations inmicroglial phenotype and function (43, 44), we provide new insights into beta-amyloidinduced alterations in APCs and T-cells, key players of brain immune surveillance.”
BackgroundPathways linking Alzheimer’s disease risk genes expressed highly in microglia
Hodges, A. K., Piers, T. M., Collier, D., Cousins, O., & Pocock, J. M. (2021) · Neuroimmunology and Neuroinflammation · doi:10.20517/2347-8659.2020.60 · Cited by 21
The NLRP3 Inflammasome in the Pathogenesis and Treatment of Alzheimer’s Disease
Golzari-Sorkheh, M., Brown, C. E., Weaver, D. F., & Reed, M. A. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210660 · Cited by 21
“Constitutive activation of the NLRP3 inflammasome by microglia in severe AD impairs microglial clearance of A (cid:2) and NFT [60].”
Hohsfield, L. A., & Humpel, C. (2015) · PLoS ONE · doi:10.1371/journal.pone.0121930 · Cited by 21
“Furthermore, several investigations have shown that alterations and functional impairments in monocytes and microglia correlate or coincide with cognitive decline and amyloid deposition in AD transgenic mice [47,48].”
BackgroundIron, Aging, and Neurodegeneration
Angelova, D. M., & Brown, D. R. (2015) · Metals · doi:10.3390/met5042070 · Cited by 23
Peña‐Ortega, F. (2019) · Current Alzheimer Research · doi:10.2174/1567205017666191213162233 · Cited by 21
Stoyanov, S., Sun, W., Düsedau, H. P., Cangalaya, C., Choi, I., Mirzapourdelavar, H., Baidoe‐Ansah, D., Kaushik, R., Neumann, J. H. L., Dunay, I. R., et al. (2020) · Glia · doi:10.1002/glia.23894 · Cited by 21
“This result contradicts the still unconfirmed hypothesis that the increased expression of immune factors underlies AD-like pathology in the early stages (Krstic et al., 2012).”
ResultTherapeutic Potential of Neu1 in Alzheimer’s Disease Via the Immune System
Khan, A., Das, S. K., & Sergi, C. M. (2021) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317521996147 · Cited by 21
“Nonetheless, as the disease progresses, microglia may lose this beneficial effect as they acquire a different phenotype due to chronic activation and continued production of pro-inflammatory mediators.(42,43)”
BackgroundSánchez-Castillo, A. I., Sepúlveda, M. R., Marín‐Teva, J. L., Cuadros, M. Á., Martín‐Oliva, D., González‐Rey, E., Delgado, M., & Neubrand, V. E. (2022) · Biomolecules · doi:10.3390/biom12020219 · Cited by 22
A Comparative Evaluation of a Novel Vaccine in APP/PS1 Mouse Models of Alzheimer’s Disease
Carrera, I., Etcheverrı́a, I., Fernández‐Novoa, L., Lombardi, V., Lakshmana, M. K., Cacabelos, R., & Vigo, C. (2015) · BioMed Research International · doi:10.1155/2015/807146 · Cited by 20
“Our immunologicalmeasurements demonstrated once again that neuroinflammation develops in an Aβdependent fashion early in the course of AD [41] and can be alleviated or reversed by interventional Aβ vaccination such as EB101.”
BackgroundHypoperfusion is a potential inducer of immunosuppressive network in Alzheimer's disease
Salminen, A. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104919 · Cited by 20
Sorrentino, S., Ascari, R., Maderna, E., Catania, M., Ghetti, B. F., Tagliavini, F., Giaccone, G., & Fede, G. D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052780 · Cited by 23
“It is known that in AD brains microglia show principally two distinct morphological phenotypes: the “reactive”/amoeboid-like M1 phenotype and the homeostatic-like morphology (M2 phenotype) [50].”
BackgroundMechanisms of NLRP3 activation and pathology during neurodegeneration
Jose, S., Groves, N. J., Roper, K. E., & Gordon, R. (2022) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2022.106273 · Cited by 22
Metadata
- Authors
- Krabbe, G., Halle, A., Matyash, V., Rinnenthal, J. L., Eom, G. D., Bernhardt, U., Miller, K. R., Prokop, S., Kettenmann, H., & Heppner, F. L.
- Affiliations
- Max Delbrück Center (DE)
- Center of Advanced European Studies and Research (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Corresponding author
- Kettenmann, Helmut
- Heppner, Frank L.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-04-08
- Volume
- 8
- Issue
- 4
- Pages
- e60921
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3620049
- OpenAlex
- W2044090829
- Cited by
- 478
- References
- 41
- Citations by year
- 2026: 15 · 2025: 29 · 2024: 31 · 2023: 25 · 2022: 44 · 2021: 56 · 2020: 40 · 2019: 41 · 2018: 38 · 2017: 38 · 2016: 33 · 2015: 39 · 2014: 34 · 2013: 13
- FWCI
- 22.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Max Planck Digital Library (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- European Commission (FP7 HEALTH)
- Deutsche Forschungsgemeinschaft (SFB TRR 43, NeuroCure EXC257, GRK1258, EXC257)
- Jung-Stiftung für Wissenschaft und Forschung
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS046006, NS046006)
- FP7 Health
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- microglia, Alzheimer's disease, amyloid plaques, microglial activation, microglial phagocytosis, mouse models of Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Animals, Cell Movement, Disease Models, Animal, Female, Humans, Male, Mice, Transgenic, Mutation, Phagocytosis, Amyloid beta-Peptides, Protein Structure, Secondary, Microglia, Mice, Protein Multimerization, Plaque, Amyloid, Spatio-Temporal Analysis
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