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Microglial Dysfunction and Defective β-Amyloid Clearance Pathways in Aging Alzheimer's Disease Mice
Open accessAbstract
Early microglial accumulation in Alzheimer's disease (AD) delays disease progression by promoting clearance of β-amyloid (Aβ) before formation of senile plaques. However, persistent Aβ accumulation despite increasing microglial numbers suggests that the ability of microglia to clear Aβ may decrease with age and progression of AD pathology. To determine the effects of aging and Aβ deposition on microglial ability to clear Aβ, we used quantitative PCR to analyze gene expression in freshly isolated adult microglia from 1.5-, 3-, 8-, and 14-month-old transgenic PS1-APP mice, an established mouse model of AD, and from their nontransgenic littermates. We found that microglia from old PS1-APP mice, but not from younger mice, have a twofold to fivefold decrease in expression of the Aβ-binding scavenger receptors scavenger receptor A (SRA), CD36, and RAGE (receptor for advanced-glycosylation endproducts), and the Aβ-degrading enzymes insulysin, neprilysin, and MMP9, compared with their littermate controls. In contrast, PS1-APP microglia had a 2.5-fold increase in the proinflammatory cytokines IL-1β (interleukin-1β) and tumor necrosis factor α (TNFα), suggesting that there is an inverse correlation between cytokine production and Aβ clearance. In support of this possibility, we found that incubation of cultured N9 mouse microglia with TNFα decreased the expression of SRA and CD36 and reduced Aβ uptake. Our data indicate that, although early microglial recruitment promotes Aβ clearance and is neuroprotective in AD, as disease progresses, proinflammatory cytokines produced in response to Aβ deposition downregulate genes involved in Aβ clearance and promote Aβ accumulation, therefore contributing to neurodegeneration. Antiinflammatory therapy for AD should take this dichotomous microglial role into consideration.
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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 [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, as AD progresses, microglia acquire a chronically activated phenotype through unremitting stimulation by cytokines and A itself, which compromises their clearance function (Bamberger et al., 2003;Hickman et al., 2008;Heneka et al., 2010a) .”
From PPARγ/RXRα-Induced and CD36-Mediated Microglial Amyloid-β Phagocytosis Results in Cognitive Improvement in Amyloid Precursor Protein/Presenilin 1 Mice (2012) · cites this paper as Hickman et al., 2008
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Progression of Alzheimer's disease is associated with reduced Aβ-clearing pathways resulting in Aβ accumulation (4–6).”
From Heterozygous CX3CR1 Deficiency in Microglia Restores Neuronal β-Amyloid Clearance Pathways and Slows Progression of Alzheimer's Like-Disease in PS1-APP Mice (2019) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Progression of Alzheimer's disease in humans and mouse models of the disease is associated with reduced expression of these Aβ-clearing enzymes resulting in decreased Aβ clearance and increased Aβ accumulation (5, 24).”
From Heterozygous CX3CR1 Deficiency in Microglia Restores Neuronal β-Amyloid Clearance Pathways and Slows Progression of Alzheimer's Like-Disease in PS1-APP Mice (2019) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This impairment has been shown to correlate with increased production of proinflammatory cytokines and overwhelming accumulation of Aβ plaques in the AD brain [20–22].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [22]
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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 [40]
The cited source says what the claim attributes to it.
In the citing paper
“Thus, endothelial expression of LRP1 promotes the clearance of Aβ across the BBB in vivo, a process directly modulated by PCSK9 inhibitor treatment (93, 94), and the expression of CD36 parallels the ability of microglia to perform Aβ clearance (95).”
From PCSK9 and the nervous system: a no-brainer? (2023) · cites this paper as [95]
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In the citing paper
“Increased pro-inflammatory gene expression in response to accumulating Αβ in older AD mice leads to decreased microglial Αβ clearance receptors or Αβ-degrading enzymes, thereby promoting further Αβ accumulation16.”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [16]
The cited source says what the claim attributes to it.
In the citing paper
“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 [16]
The cited source says what the claim attributes to it.
In the citing paper
“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 [16]
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“As one of the most relevant consequences, the loss of microglial phagocytic capacity leads to further Aβ accumulation and aggregation, accelerating the progression of AD [17].”
From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [17]
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In the citing paper
“We have previously shown that expression of IDE in microglia from PS1-APP mice decreases with age and progression of AD-like pathology (5).”
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Finally, Inpp5d was identified as a target of miR155, and constitutive deletion of miR155, which should increase SHIP1, led to an increase in amyloid plaques.40,41”
From Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [40]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Finally, Inpp5d was identified as a target of miR155, and constitutive deletion of miR155, which should increase SHIP1, led to an increase in amyloid plaques.40,41”
From Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [40]
Experimental — accuracy not yet measuredIn the citing paper
“Aged glial cells respond less efficiently to antigens, including amyloid-β (Aβ) and α-synuclein, and have reduced phagocytic and antiinflammatory capacity (161–163).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [161]
In the citing paper
“AD is accompanied by activation of microglia and astrocytes1,2 that affects the clearance and production of Aβ42,3,4 development and propagation of tau pathology,5 exacerbates neurodegeneration, and influences disease progression and severity.6,7”
From CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease (2018) · cites this paper as [3]
In the citing paper
“microglia from a mouse model of Aβ deposition (Aβ-mice) have reduced expression of Aβ-phagocytic receptors and Aβ-degrading enzymes, but their ability to produce proinflammatory cytokines was maintained6.”
From Microglia in neurodegeneration (2018) · cites this paper as [6]
In the citing paper
“In response to such stimuli, microglia can initiate a neuroinflammatory response which, like peripheral inflammation, includes production of cytokines such as TNF and IL-16,27, and possibly chemokines such as Ccl228, to recruit additional cells and induce them to clear injurious agents and maintain brain homeostasis.”
From Microglia in neurodegeneration (2018) · cites this paper as [6]
In the citing paper
“Aβ clearance involves, in part36, phagocytosis and endocytosis via microglial scavenger receptors (SRs)37,38 and extracellular degradation by Aβ-degrading enzymes6,36.”
From Microglia in neurodegeneration (2018) · cites this paper as [6]
In the citing paper
“Despite effective uptake, Aβ clearance by microglia in AD may be ineffective despite phagocytic uptake [55].”
From Identification and therapeutic modulation of a pro-inflammatory subset of disease-associated-microglia in Alzheimer’s disease (2018) · cites this paper as [55]
In the citing paper
“In AD, microglia cluster around beta-amyloid plaques highlighting their inability to clear beta-amyloid (Hickman et al., 2008; Liu et al., 2010).”
From iPSC-derived human microglia-like cells to study neurological diseases (2017) · cites this paper as Hickman et al., 2008
In the citing paper
“Immune involvement in neurodegenerative disease centres on findings that pro-inflammatory microglia are closely associated with protein aggregate pathologies characteristic of most dementias.”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [13]
In the citing paper
“In Alzheimer’s disease (AD), the most common form of dementia, microglia surround amyloid plaques and respond to amyloid-β with a pro-inflammatory phenotype characterised by cytokine expression (e.g., interleukins (IL) 1β and 6 and tumour necrosis factor α (TNFα)) that may initially limit amyloidosis but likely becomes overzealous and neurotoxic [12,13,14].”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [13]
In the citing paper
“For example, PS1-APP mice (a model of Alzheimer's Disease) showed an age-dependent reduction in receptors and enzymes involved in beta amyloid degradation, although still maintaining elevated levels of cytokine (Hickman et al, 2008).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Hickman et al, 2008
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Citations
Cites
RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease
Yan, S. D., Chen, X., Fu, J., Chen, M., Zhu, H., Roher, A., Slattery, T., Zhao, L., Nagashima, M., Morser, J., et al. (1996) · Nature · doi:10.1038/382685a0 · Cited by 2,012 · cited 5×
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BackgroundInfluentialJankowsky, J. L., Fadale, D. J., Anderson, J., Xu, G. M., Gonzales, V., Jenkins, N. A., Copeland, N. G., Lee, M. K., Younkin, L. H., Wagner, S. L., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh019 · Cited by 1,575 · cited 1×
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BackgroundActivation of microglial cells by β-amyloid protein and interferon-γ
Meda, L., Cassatella, M. A., Szendrei, G. I., Otvos, L., Baron, P., Villalba, M., Ferrari, D., & Rossi, F. (1995) · Nature · doi:10.1038/374647a0 · Cited by 1,314
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“…receptors that promote the clearance and phagocytosis of A , such as class A scavenger receptor, CD36, and receptor for advanced-glycosylation endproducts (RAGE) (Yan et al., 1996; El Khoury et al., 1998), and microglia can restrict senile plaque formation by phagocytosing A (Simard et al., 2006).”
BackgroundBorchelt, D. R., Ratovitski, T., van Lare, J., Lee, M. K., Gonzales, V., Jenkins, N. A., Copeland, N. G., Price, D. L., & Sisodia, S. S. (1997) · Neuron · doi:10.1016/s0896-6273(00)80974-5 · Cited by 1,023 · cited 2×
“To investigate this hypothesis, we developed a method to isolate fresh adult mouse microglia from the bigenic APPswe/PSEN1dE9 (PS1-APP) mice (Borchelt et al., 1997; Jankowsky et al., 2001), a robust mouse model of AD, and from their nontransgenic littermates at various ages and stages of AD-like…”
El Khoury, J., Toft, M., Hickman, S. E., Means, T. K., Terada, K., Geula, C., & Luster, A. D. (2007) · Nature Medicine · doi:10.1038/nm1555 · Cited by 915 · cited 5×
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“Microglia, the mononuclear phagocytes of the brain (Perry and Gordon, 1988), accumulate in senile plaques in AD patients and in animal models of AD (McGeer et al., 1987; Perlmutter et al., 1990; Frautschy et al., 1998; Dickson, 1999; Stalder et al., 1999).”
Macrophages and microglia in the nervous system
Perry, V. H., & Gordon, S. (1988) · Trends in Neurosciences · doi:10.1016/0166-2236(88)90110-5 · Cited by 747 · cited 2×
“Microglia, the mononuclear phagocytes of the brain (Perry and Gordon, 1988), accumulate in senile plaques in AD patients and in animal models of AD (McGeer et al.”
Co-expression of multiple transgenes in mouse CNS: a comparison of strategies
Jankowsky, J. L., Slunt, H. H., Ratovitski, T., Jenkins, N. A., Copeland, N. G., & Borchelt, D. R. (2001) · Biomolecular Engineering · doi:10.1016/s1389-0344(01)00067-3 · Cited by 746 · cited 3×
“…hypothesis, we developed a method to isolate fresh adult mouse microglia from the bigenic APPswe/PSEN1dE9 (PS1-APP) mice (Borchelt et al., 1997; Jankowsky et al., 2001), a robust mouse model of AD, and from their nontransgenic littermates at various ages and stages of AD-like pathology, and…”
Scavenger receptor-mediated adhesion of microglia to β-amyloid fibrils
Khoury, J. E., Hickman, S. E., Thomas, C. A., Cao, L., Silverstein, S. C., & Loike, J. D. (1996) · Nature · doi:10.1038/382716a0 · Cited by 727 · cited 2×
“N9 mouse microglia (a gift from Dr. P. Riciarrdi-Castagnoli, University of Milan, Bicocca, Italy) (El Khoury et al., 1996) were plated on 24-well plates coated with 1 g of fibronectin/ cm 2 (Sigma-Aldrich), and grown overnight in RPMI 1640 supplemented with10% FBS, L-glutamine (2 mM), penicillin…”
BackgroundMethodSelf-citation
Cited by
Sorted by citations
Items 201–300 of 1,003
Microglial dysfunction connects depression and Alzheimer’s disease
Santos, L. E., Beckman, D., & Ferreira, S. T. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.11.011 · Cited by 154
“These cytokines may, in turn, downregulate microglial enzymes, further impairing Ab clearance (Hickman et al., 2008; Orre et al., 2014).”
BackgroundMemory decline accompanies subthreshold amyloid accumulation
Landau, S. M., Horng, A., Jagust, W. J., & Initiative, A. D. N. (2018) · Neurology · doi:10.1212/wnl.0000000000005354 · Cited by 150
“Negative slopes in baselinenegative nonaccumulators presumably reflect measurement noise, although the possibility that Aβ clearance contributes to negative slopes is conceivable.(27,28) The mean slope of baseline-negative nonaccumulators was −0.”
BackgroundThe Important Interface Between Apolipoprotein E and Neuroinflammation in Alzheimer’s Disease
Kloske, C. M., & Wilcock, D. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00754 · Cited by 152
Amyloid-β-Induced Astrocytic Phagocytosis is Mediated by CD36, CD47 and RAGE
Jones, R. S., Minogue, A. M., Connor, T. J., & Lynch, M. A. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-012-9427-3 · Cited by 147
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“Microglia lose their phagocytic activity gradually during the progression of AD [13, 14], and this process is also highly sensitive to inflammatory”
BackgroundFibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models
Sebastian Monasor, L., Müller, S. A., Colombo, A. V., Tanrioever, G., König, J., Roth, S., Liesz, A., Berghofer, A., Piechotta, A., Prestel, M., et al. (2020) · eLife · doi:10.7554/elife.54083 · Cited by 147
“It has also been shown that microglial phagocytosis decays over the course of AD (Hickman et al., 2008; Koellhoffer et al., 2017; Orre et al., 2014a; Solito and Sastre, 2012; Zuroff et al., 2017).”
Glial cells in Alzheimer’s disease: From neuropathological changes to therapeutic implications
Uddin, M. S., & Lim, L. W. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101622 · Cited by 154
Long-term immunomodulatory effect of amniotic stem cells in an Alzheimer's disease model
Kim, K.-S., Kim, H. S., Park, J.-M., Kim, H. W., Park, M., Lee, H., Lim, D. S., Lee, T. H., Chopp, M., & Moon, J. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.03.029 · Cited by 144
“However, increased levels of proinflammatory cytokines such as TNF-a and IL-1 cause a deterioration in the protective ability of the microglia as AD progresses (Hickman et al., 2008), and therefore the changes of inflammatory cytokine secretion and microglial activation after AMSC injection were investigated.”
BackgroundDystrophic microglia in late‐onset Alzheimer's disease
Streit, W. J., Khoshbouei, H., & Bechmann, I. (2020) · Glia · doi:10.1002/glia.23782 · Cited by 152
Ma, T., Gong, K., Ao, Q., Yan, Y., Song, B., Huang, H., Zhang, X., & Gong, Y. (2013) · Cell Transplantation · doi:10.3727/096368913x672181 · Cited by 146
Potassium Channel Kv1.3 Is Highly Expressed by Microglia in Human Alzheimer's Disease
Rangaraju, S., Gearing, M., Jin, L.-W., & Levey, A. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-141704 · Cited by 137
“It is suggested that early microglial activation in AD has a neuroprotective effect by promoting clearance of amyloid-β (Aβ, however, in the later stages pro-inflammatory cytokines produced by activated microglia have detrimental effects that promote neurodegeneration [3].”
BackgroundMicroglial activation states and their implications for Alzheimer's Disease
Valiukas, Z., Tangalakis, K., Apostolopoulos, V., & Feehan, J. (2025) · The Journal of Prevention of Alzheimer s Disease · doi:10.1016/j.tjpad.2024.100013 · Cited by 167
The Emerging Role of Central and Peripheral Immune Systems in Neurodegenerative Diseases
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“On the one hand, continuous stimulation with high cytokine concentrations leads to the transformation of microglia into a dysfunctional senescent state, with diminished phagocytosis leading to Aβ accumulation and the loss of neural support functions (Hickman et al., 2008; Salani et al., 2019).”
BackgroundEvolution of neuroinflammation across the lifespan of individuals with Down syndrome
Flores-Aguilar, L., Iulita, M. F., Kovecses, O., Torres, M. D., Levi, S. M., Zhang, Y., Askenazi, M., Wisniewski, T., Busciglio, J., & Cuello, A. C. (2020) · Brain · doi:10.1093/brain/awaa326 · Cited by 138
“…in adult Down syndrome brains may represent a compensatory attempt to promote amyloid-b clearance, this might be an unlikely scenario given that defective microglial phagocytosis has been reported at late stages of Alzheimer’s disease (Hickman et al., 2008; Mawuenyega et al., 2010).”
BackgroundDifferential cell proliferation in the cortex of the appsweps1de9 alzheimer's disease mouse model
Kamphuis, W., Orre, M., Kooijman, L., Dahmen, M., & Hol, E. M. (2012) · Glia · doi:10.1002/glia.22295 · Cited by 137
“Similar observations in APPswePS1dE9 and other AD models have been reported (Hickman et al., 2008; Jimenez et al., 2008; Ruan et al., 2009; Shaftel et al., 2007; Wirths et al., 2010).”
BackgroundResultInfluentialKocherhans, S., Madhusudan, A., Doehner, J., Breu, K. S., Nitsch, R. M., Fritschy, J.-M., & Knuesel, I. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0418-10.2010 · Cited by 132
“…data also fit with recent findings showing that the phenotype of accumulating microglia changes as AD-like pathology progresses in tgAPP-PS1 mice (Hickman et al., 2008), from a protective, A -clearing role during early phases to an enhanced production in inflammatory cytokine and loss in A…”
BackgroundResultThe role of microglia in human disease: therapeutic tool or target?
Cartier, N., Lewis, C. B., Zhang, R., & Rossi, F. M. V. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1330-y · Cited by 142
Neuroinflammation and fractalkine signaling in Alzheimer’s disease
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“[43] observed reduced gene expression of amyloid beta-binding”
Drug development for alzheimer’s disease: Microglia induced neuroinflammation as a target
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“In sporadic AD, reduced Aβ clearance can be linked with insufficient microglial phagocytic capacity, which is characterized by the down-regulation of Aβ phagocytosis receptors and increased cytokine concentrations [94,95].”
BackgroundTao, L., Liu, Q., Zhang, F., Fu, Y., Zhu, X. D., Weng, X., Han, H., Huang, Y., Suo, Y., Chen, L., et al. (2021) · Light Science & Applications · doi:10.1038/s41377-021-00617-3 · Cited by 133
Inflammatory aspects of Alzheimer’s disease
Lucena, P. B., & Heneka, M. T. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02790-2 · Cited by 152
“APP/PS1 mice have a twofold-to-fivefold decrease in expression of the Aβ-binding scavenger receptors scavenger receptor A (SRA), CD36, and RAGE, and the Aβ-degrading enzymes insulysin, neprilysin, and MMP9, compared with their littermate controls [98].”
Microglial Malfunction: The Third Rail in the Development of Alzheimer's Disease
Mhatre, S. D., Tsai, C. A., Rubin, A. J., James, M. L., & Andreasson, K. I. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.08.006 · Cited by 134
“However, exposure to accumulating Ab peptides leads to loss of these crucial microglial functions, resulting in a persistent proinflammatory state and failure to clear misfolded proteins [92,93].”
Maezawa, I., Nguyen, H. M., Di Lucente, J., Jenkins, D. P., Singh, V., Hilt, S., Kim, K., Rangaraju, S., Levey, A. I., Wulff, H., et al. (2018) · Brain · doi:10.1093/brain/awx346 · Cited by 125
“In our experiments, PAP-1 was administered to APP/PS1 mice at an age when microglia amyloid-b clearance capacity was impaired (Hickman et al., 2008).”
BackgroundMethodInfluentialThe endocytic pathway in microglia during health, aging and Alzheimer’s disease
Solé-Domènech, S., Cruz, D. L., Capetillo-Zarate, E., & Maxfield, F. R. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.07.002 · Cited by 133
Progranulin Mutations as Risk Factors for Alzheimer Disease
Perry, D. C., Lehmann, M., Yokoyama, J. S., Karydas, A., Lee, J. J., Coppola, G., Grinberg, L. T., Geschwind, D. H., Seeley, W. W., Miller, B. L., et al. (2013) · JAMA Neurology · doi:10.1001/2013.jamaneurol.393 · Cited by 133
“Whether this activity is detrimental or protective and primary or secondary has been debated, but there is evidence suggesting that high levels of proinflammatory cytokines might decrease phagocytosis of A by microglia.(27) An increase in TNF- is associated with cognitive decline in AD.”
BackgroundKrabbe, G., Minami, S., Etchegaray, J. I., Taneja, P., Djukic, B., Davalos, D., Le, D., Lo, I., Zhan, L., Reichert, M. C., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1700477114 · Cited by 137
Heat-Shock Proteins in Neuroinflammation
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“This negative correlation between the expressions of IL-1β, TNF-α, and Aβ clearance generates neuronal damage (Hickman et al., 2008; Figure 1B).”
BackgroundBoyd, T. D., Bennett, S. P., Mori, T., Governatori, N., Runfeldt, M., Norden, M., Padmanabhan, J., Neame, P., Wefes, I., Sanchez-Ramos, J., et al. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-091471 · Cited by 128
“4), implying an augmentedability to bind and removeamyloid deposition [27,28].”
Pinto, S., Cunha, C., Barbosa, M., Vaz, A. R., & Brites, D. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00273 · Cited by 135
“Decreased phagocytic ability was demonstrated for senescent microglia in aging and in Alzheimer’s disease models (Hickman et al., 2008; Zhu et al., 2011; Caldeira et al., 2014).”
BackgroundChoi, S., Aïd, S., Caracciolo, L., Minami, S., Niikura, T., Matsuoka, Y., Turner, R. S., Mattson, M. P., & Bosetti, F. (2012) · Journal of Neurochemistry · doi:10.1111/jnc.12059 · Cited by 136
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Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging
Condello, C., Yuan, P., & Grutzendler, J. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.10.007 · Cited by 131
“In addition, aging microglia may be less phagocytic and adopt an activated phenotype with release of proinflammatory cytokines (108), and a reduction in anti-inflammatory cytokines such as transforming growth factor-b (109).”
Sex dimorphism profile of Alzheimer’s disease-type pathologies in an APP/PS1 mouse model
Jiao, S.-S., Bu, X.-L., Liu, Y.-H., Zhu, C., Wang, Q.-H., Shen, L.-L., Liu, C.-H., Wang, Y.-R., Yao, X.-Q., & Wang, Y.-J. (2016) · Neurotoxicity Research · doi:10.1007/s12640-015-9589-x · Cited by 129
“Sex discrepancy in neuroinflammation may be a downstream event secondary to that in Ab burden, as neuroinflammation have been described as a local cellular response to Ab release and deposition (Hickman et al. 2008).”
Pey, P., Pearce, R. K., Kalaitzakis, M. E., Griffin, W. S. T., & Gentleman, S. M. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-21 · Cited by 128
“via downregulation of Aβ receptors [22] and neuronal degeneration, but TNF-α is protective due to its pre-conditioning effect on metabolic excitotoxicity, Aβ toxicity and ischaemia [23].”
BackgroundShadfar, S., Hwang, C. J., Lim, M., Choi, D., & Hong, J. T. (2015) · Archives of Pharmacal Research · doi:10.1007/s12272-015-0648-x · Cited by 136
“The clearance function declines with age, so accumulation of plaques continues in spite of increasing microglial numbers (Hickman et al. 2008).”
BackgroundPiirainen, S., Youssef, A. M., Song, C., Kalueff, A. V., Landreth, G. E., Malm, T., & Tian, L. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.01.046 · Cited by 130
“hile microglia play a pivotal role in A phagocytosis and clearnce (Gandy and Heppner, 2013; Hickman et al., 2008), persistent icroglial pro-inflammatory activation exacerbates amyloidosis, euronal damage and neuroinflammation (Heppner et al.”
Kong, Y., Ruan, L., Qian, L., Liu, X., & Le, Y. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2985-10.2010 · Cited by 128
“Activation of microglia leads to uptake and clearance of amyloid peptide (A ) (Frautschy et al., 1998; Qiu et al., 1998; Simard et al., 2006; Hickman et al., 2008).”
BackgroundMicroglia in Aging and Alzheimer’s Disease: A Comparative Species Review
Edler, M. K., Mhatre-Winters, I., & Richardson, J. R. (2021) · Cells · doi:10.3390/cells10051138 · Cited by 126
Targeting innate immunity for neurodegenerative disorders of the central nervous system
Andreasson, K. I., Bachstetter, A. D., Colonna, M., Ginhoux, F., Holmes, C., Lamb, B., Landreth, G., Lee, D. C., Low, D., Lynch, M. A., et al. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13667 · Cited by 126
Microglial phagocytosis in aging and Alzheimer's disease
Gabandé‐Rodríguez, E., Keane, L., & Capasso, M. (2020) · Journal of Neuroscience Research · doi:10.1002/jnr.24419 · Cited by 127
Microglia-derived extracellular vesicles in Alzheimer’s Disease: A double-edged sword
Trotta, T., Antonietta Panaro, M., Cianciulli, A., Mori, G., Di Benedetto, A., & Porro, C. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.12.020 · Cited by 126
“Gao et al. discovered that GAPDH interacts with TNF receptorassociated factor2 (TRAF2) to promote TNFa-mediated activation of NF-kB and regulation of TRAF2 polyubiquitination [141].”
InfluentialTeter, B., Morihara, T., Lim, G. P., Chu, T., Jones, M. R., Zuo, X., Paul, R. M., Frautschy, S. A., & Cole, G. M. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.02.015 · Cited by 127
“Although initial Aβ aggregates are effectively cleared by innate immune microglia (Lucin et al., 2013; Rogers et al., 2002), clearance fails with chronic inflammation and the onset of amyloid plaques (Hickman et al., 2008; Krabbe et al., 2013).”
BackgroundCrosstalk Between Dysfunctional Mitochondria and Inflammation in Glaucomatous Neurodegeneration
Jassim, A. H., Inman, D. M., & Mitchell, C. H. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.699623 · Cited by 126
Sui, D.-M., Xie, Q., Yi, W.-J., Gupta, S., Yu, X.-Y., Li, J.-B., Wang, J., Wang, J.-F., & Deng, X.-M. (2016) · Mediators of Inflammation · doi:10.1155/2016/1045657 · Cited by 124
“The accumulation of amyloidβ can activate NLRP3 in microglia, while the increased maturation of IL-1β further hampered the clearance of amyloidβ by microglia [29].”
BackgroundRAGE regulates BACE1 and Aβ generation via NFAT1 activation in Alzheimer's disease animal model
Cho, H. J., Son, S. M., Jin, S. M., Hong, H. S., Shin, D. H., Kim, S. J., Huh, K. H., & Mook‐Jung, I. (2009) · The FASEB Journal · doi:10.1096/fj.08-126383 · Cited by 124
Glioblastoma hijacks microglial gene expression to support tumor growth
Maas, S. L. N., Abels, E. R., van de Haar, L. L., Zhang, X., Morsett, L. M., Sil, S., Guedes, J. R., Sen, P., Prabhakar, S., Hickman, S. E., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01797-2 · Cited by 128
“For FACS, we generated highly enriched microglia, monocyte, and macrophage populations from the brains of tumor-bearing and control mice using an established protocol for cell dissociation, isolation, and analysis [26, 33, 34].”
MethodSelf-citationMechanisms of NLRP3 Inflammasome Activation: Its Role in the Treatment of Alzheimer’s Disease
Zhang, Y., Zhao, Y., Zhang, J., & Yang, G. (2020) · Neurochemical Research · doi:10.1007/s11064-020-03121-z · Cited by 127
Baligács, N., Albertini, G., Borrie, S. C., Serneels, L., Pridans, C., Balusu, S., & De Strooper, B. (2024) · Nature Communications · doi:10.1038/s41467-024-54779-w · Cited by 123
“On one hand, microglia are believed to facilitate amyloid clearance through phagocytosis, potentially limiting plaque pathology 11 – 13 .”
Handattu, S. P., Garber, D. W., Monroe, C. E., van Groen, T., Kadish, I., Nayyar, G., Cao, D., Palgunachari, M. N., Li, L., & Anantharamaiah, G. M. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.03.007 · Cited by 125
“Hickman et al. (2008) have used the same mouse model as we have used in this study and shown that, as these mice age, there is increased expression of IL-1β and TNF-α, showing that microglia in aged AD mice retain their pro-inflammatory response in the presence of continued Aβ deposition.”
MethodYang, G., Meng, Y. J., Li, W., Yong, Y., Fan, Z., Ding, H., Wei, Y., Luo, J., & Ke, Z. (2010) · Brain Pathology · doi:10.1111/j.1750-3639.2010.00445.x · Cited by 124
“The accumulation and the activation of microglia are implicated in the pathogenesis of Alzheimer’s disease (AD) (5, 12, 27, 37), Parkinson’s disease (PD) (50), autism (64) and retina detachment (48); the activated microglia specifically distribute in affected regions.”
BackgroundAhmed, M. E., Iyer, S. S., Thangavel, R., Kempuraj, D., Selvakumar, G. P., Raikwar, S. P., Zaheer, S. A., & Zaheer, A. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170634 · Cited by 120
“However, with the progression of AD, glial cells get adapted to cytokines deposition, which disturbs the microglial clearance function [24, 25].”
Systemic inflammation linking chronic periodontitis to cognitive decline
Wang, R. P., Ho, J. Y. S., Leung, W. K., Goto, T., & Chang, R. C. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.07.002 · Cited by 129
Scheiblich, H., Bousset, L., Schwartz, S., Griep, A., Latz, E., Melki, R., & Heneka, M. T. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2100035 · Cited by 122
“In response to persistent neurodegeneration, microglia adopt a chronically activated phenotype resulting in the sustained release of cytokines, including IL-1b, that have been found to impair its own clearance functions (57).”
BackgroundMicroglia in Alzheimer’s disease: A multifaceted relationship
ElAli, A., & Rivest, S. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.07.021 · Cited by 134
“However, in contrast to the early stages of AD, Aβ clearance by microglia seems very slow and ineffective in the late stages (El Khoury et al., 2007; Hickman et al., 2008).”
BackgroundInfluentialGriciuc, A., Federico, A. N., Natasan, J.-S., Forte, A. M., McGinty, D., Nguyen, H., Volak, A., LeRoy, S. G., Gandhi, S., Lerner, P., et al. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa179 · Cited by 128
Nicotinic Acetylcholine Receptor Agonists for the Treatment of Alzheimer’s Dementia: An Update
Hoskin, J. L., Al-Hasan, Y. M., & Sabbagh, M. N. (2018) · Nicotine & Tobacco Research · doi:10.1093/ntr/nty116 · Cited by 128
Baron, R., Babcock, A. A., Nemirovsky, A., Finsen, B., & Monsonego, A. (2014) · Aging Cell · doi:10.1111/acel.12210 · Cited by 118
“Indeed, microglia are more abundant at sites of Ab plaques, with altered morphology reminiscent of cell activation (Mucke et al., 2000; Hickman et al., 2008; Eisenberg & Jucker, 2012).”
BackgroundMitochondrial Regulation of Microglial Immunometabolism in Alzheimer’s Disease
Fairley, L. H., Wong, J. H., & Barron, A. M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.624538 · Cited by 120
“They can mitigate neurodegeneration through phagocytic clearance of pathological Ab (2, 13) and tau (14), by removing dying neurons thus preventing “bystander” neuronal death (15, 16) and releasing neurotrophic factors promoting neuronal support including nerve growth factor, brain-derived neurotrophic factor, and ins…”
BackgroundXu, J., & Ikezu, T. (2008) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-008-9136-0 · Cited by 120
“IL-1β may also impair the microglia-mediated Aβ clearance (Hickman et al. 2008).”
BackgroundMicrobial involvement in Alzheimer disease development and progression
Bulgart, H. R., Neczypor, E. W., Wold, L. E., & Mackos, A. R. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00378-4 · Cited by 116
Phagocyte dysfunction, tissue aging and degeneration
Li, W. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2013.05.006 · Cited by 116
Lee, J. K., Schuchman, E. H., Jin, H. K., & Bae, J. (2012) · Stem Cells · doi:10.1002/stem.1125 · Cited by 121
Yanguas‐Casás, N., Crespo‐Castrillo, A., CEBALLOS, M. L. D., Chowen, J. A., Azcoitia, Í., Arévalo, M., & García‐Segura, L. M. (2017) · Glia · doi:10.1002/glia.23263 · Cited by 126
Microbiota modulation as preventative and therapeutic approach in Alzheimer’s disease
Bonfili, L., Cecarini, V., Gogoi, O., Gong, C., Cuccioloni, M., Angeletti, M., Rossi, G., & Eleuteri, A. M. (2020) · FEBS Journal · doi:10.1111/febs.15571 · Cited by 123
Immune Response in Neurological Pathology: Emerging Role of Central and Peripheral Immune Crosstalk
Passaro, A. P., Lebos, A. L., Yao, Y., & Stice, S. L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.676621 · Cited by 124
Mallick, R., Basak, S., & Duttaroy, A. K. (2021) · Progress in Lipid Research · doi:10.1016/j.plipres.2021.101116 · Cited by 126
Amyloid-β oligomers in cellular models of Alzheimer’s disease
Fontana, I. C., Zimmer, A. R., Rocha, A. S., Gosmann, G., Souza, D. O., Lourenco, M. V., Ferreira, S. T., & Zimmer, E. R. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15030 · Cited by 115
Guedes, J. R., Lao, T., Cardoso, A. L., & El Khoury, J. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00549 · Cited by 115
Microglia-Astrocyte Communication in Alzheimer’s Disease
Wu, Y., & Eisel, U. L. M. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230199 · Cited by 125
Kofler, J., & Wiley, C. A. (2010) · Toxicologic Pathology · doi:10.1177/0192623310387619 · Cited by 122
Assessing the contribution of inflammation in models of Alzheimer's disease
Johnston, H. R., Boutin, H., & Allan, S. M. (2011) · Biochemical Society Transactions · doi:10.1042/bst0390886 · Cited by 114
Astrocytes and neuroinflammation in Alzheimer's disease
Phillips, E. C., Croft, C. L., Crane, K., O’Neill, M. J., Hutton, M. L., Hanger, D. P., Garwood, C. J., & Noble, W. J. (2014) · Biochemical Society Transactions · doi:10.1042/bst20140155 · Cited by 115
Liu, B., Le, K. X., Park, M.-A., Wang, S., Belanger, A. P., Dubey, S., Frost, J. L., Holton, P., Reiser, V., Jones, P. A., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.0996-15.2015 · Cited by 114
“Initially, neuroinflammatory responses may be a self-defense mechanism to protect the brain during disease and injury (Meda et al., 2001; Morgan et al., 2005; Tuppo and Arias, 2005; Hickman et al., 2008; Winkeler et al., 2010).”
BackgroundWoodling, N. S., Wang, Q., Priyam, P. G., Larkin, P. B., Shi, J., Johansson, J. U., Zagol-Ikapitte, I. A., Boutaud, O. G., & Andreasson, K. I. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0410-14.2014 · Cited by 117
“EP4 receptor signaling potentiates phagocytosis of A Previous studies have found that inflammatory cytokines such as TNF- reduce the ability of microglia to effectively phagocytose and clear A (El Khoury et al., 2003; Hickman et al., 2008).”
BackgroundKawahara, K., Suenobu, M., Yoshida, A., Koga, K., Hyodo, A., Ohtsuka, H., Kuniyasu, A., Tamamaki, N., Sugimoto, Y., & Nakayama, H. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.01.049 · Cited by 113
“The reason for this finding has been suggested to be, in part, the inhibition of their phagocytic ability by a chronic inflammatory environment (Koenigsknecht-Talboo and Landreth, 2005; Hickman et al., 2008).”
Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice
Kyrkanides, S., Tallents, R. H., Miller, J. H., Olschowka, M. E., Johnson, R. E., Yang, M., Olschowka, J. A., Brouxhon, S. M., & O’Banion, M. K. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-112 · Cited by 116
“Alternatively, neuroinflammatory signals might limit the capacity of microglia and other cells to clear Ab plaques [45].”
BackgroundFingolimod modulates multiple neuroinflammatory markers in a mouse model of Alzheimer’s disease
Aytan, N., Choi, J., Carreras, I., Brinkmann, V., Kowall, N. W., Jenkins, B. G., & Dedeoglu, A. (2016) · Scientific Reports · doi:10.1038/srep24939 · Cited by 111
Xu, H., Gelyana, E., Rajsombath, M., Yang, T., Li, S., & Selkoe, D. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.1023-16.2016 · Cited by 109
“In AD and models thereof, microglial function can be impaired by A (Hickman et al., 2008; Krabbe et al., 2013) and by certain AD-linked genetic variants (Kleinberger et al.”
BackgroundSilverberg, G. D., Miller, M. C., Messier, A. A., Majmudar, S., Machan, J. T., Donahue, J. E., Stopa, E. G., & Johanson, C. E. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181c8ad2f · Cited by 111
“For example, RAGE expression in heart muscle is downregulated with age (25), and in an aging AD mouse model, microglial RAGE expression decreases as AA increases (60).”
BackgroundDual Role of Superoxide Dismutase 2 Induced in Activated Microglia
Ishihara, Y., Takemoto, T., Itoh, K., Ishida, A., & Yamazaki, T. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.659151 · Cited by 113
“Notably, neuroinflammation is closely linked to the onset and/or development of these CNS diseases (1-5).”
InfluentialImaging of neuroinflammation in dementia: a review
Stefaniak, J. D., & O'Brien, J. T. (2015) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2015-311336 · Cited by 113
The anti-inflammatory Annexin A1 induces the clearance and degradation of the amyloid-β peptide
Ries, M., Loiola, R. A., Shah, U. N., Gentleman, S., Solito, E., & Sastre, M. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0692-6 · Cited by 106
“inflammatory molecules [33, 34] and increasing Aβ phagocytosis.”
TRPM2 dependence of ROS-induced NLRP3 activation in Alzheimer's disease
Aminzadeh, M., Roghani, M., Sarfallah, A., & Riazi, G. H. (2017) · International Immunopharmacology · doi:10.1016/j.intimp.2017.10.024 · Cited by 110
Systemic and CNS Inflammation Crosstalk: Implications for Alzheimer’s Disease
Paouri, E., & Georgopoulos, S. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190321154618 · Cited by 109
Loss of NPC1 enhances phagocytic uptake and impairs lipid trafficking in microglia
Colombo, A. V., Dinkel, L., Müller, S. A., Monasor, L. S., Schifferer, M., Cantuti‐Castelvetri, L., König, J., Vidatic, L., Brémovà-Ertl, T., Lieberman, A. P., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21428-5 · Cited by 115
Shibuya, Y., Chang, C. C. Y., Huang, L.-H., Bryleva, E. Y., & Chang, T.-Y. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.2567-14.2014 · Cited by 108
“Impaired microglial clearance of A is partially responsible for AD pathogenesis (Hickman et al., 2008; Griciuc et al., 2013; Lucin et al., 2013).”
BackgroundHabtemariam, S. (2019) · Molecules · doi:10.3390/molecules24081519 · Cited by 115
Inflammation and Alzheimer’s Disease: Mechanisms and Therapeutic Implications by Natural Products
Rather, M. A., Khan, A., Alshahrani, S., Rashid, H., Qadri, M. M., Rashid, S., Alsaffar, R. M., Kamal, M. A., & Rehman, M. U. (2021) · Mediators of Inflammation · doi:10.1155/2021/9982954 · Cited by 114
“Microglial cells are the prime components in the system which play a critical role in the inflammatory responses, but the abnormal microglia-specific NLRP3 activation may trigger chronic neuroinflammation [166].”
Xia, Y., Xiao, Y., Wang, Z.-H., Liu, X., Alam, A. M., Haran, J. P., McCormick, B. A., Shu, X., Wang, X., & Ye, K. (2023) · Nature Communications · doi:10.1038/s41467-023-41283-w · Cited by 108
“In parallel with the progression of pathology in AD model mice, microglia also develop a more toxic in fl ammatory phenotype 44 , leading to a damaging feed-forward cycle, with increasing buildup of toxic A β peptide assemblies along with escalated toxic cytokines.”
Cai, Y., Zhang, Y., Leng, S., Ma, Y., Jiang, Q., Wen, Q., Ju, S., & Hu, J. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106426 · Cited by 120
“…activation may serve to eliminate A β ; however, chronic microglial activation can amplify the amyloid cascade and lead to neurotoxicity (Hansen et al., 2018; Joshi et al., 2014; Verkhratsky et al., 2010; Tuppo and Arias, 2005; Morgan et al., 2005; Meda et al., 2001; Hickman et al., 2008).”
Hippocampal expression of murine IL-4 results in exacerbation of amyloid deposition
Chakrabarty, P., Tianbai, L., Herring, A., Ceballos-Diaz, C., Das, P., & Golde, T. E. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-36 · Cited by 116
“inhibit Aβ uptake [35].”
Kiyota, T., Yamamoto, M., Xiong, H., Lambert, M. P., Klein, W. L., Gendelman, H. E., Ransohoff, R. M., & Ikezu, T. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006197 · Cited by 114
“Age-related microglial dysfunction for amyloid clearance also correlates with enhanced expression of proinflammatory cytokines and reduced phagocytosis [4].”
BackgroundZádori, D., Veres, G., Szalárdy, L., Klivènyi, P., & Vécsei, L. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170929 · Cited by 108
Nava-Mesa, M. O., Jiménez‐Díaz, L., Yajeya, J., & Navarro‐López, J. D. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00167 · Cited by 106
“Some of these proposals include a cascade of reactions that could involve the blockade of the glutamate recruitment by microglia (Hickman et al., 2008), alteration of the glutamatergic neurotransmission (Ashenafi et al., 2005; Santos-Torres et al., 2007), or modification of both glutamate…”
BackgroundRestoring regulatory T-cell dysfunction in Alzheimer’s disease through ex vivo expansion
Faridar, A., Thome, A. D., Zhao, W., Thonhoff, J. R., Beers, D. R., Pascual, B., Masdeu, J. C., & Appel, S. H. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa112 · Cited by 107
“…is important for containing and phagocyting amyloid plaques and for sustaining neuronal survival, chronic stimulation in combination with genetic susceptibility skews these cells towards a defective subtype (Hickman et al., 2008; Daria et al., 2017; Kang et al., 2018; Nordengen et al., 2019).”
BackgroundJung, B.-K., Pyo, K., Shin, K. Y., Hwang, Y. S., Lim, H., Lee, S. J., Moon, J.-H., Lee, S. H., Suh, Y., Chai, J.-Y., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033312 · Cited by 108
The role and therapeutic potential of monocytic cells in Alzheimer's disease
Malm, T., Koistinaho, M., Muona, A., Magga, J. M., & Koıstınaho, J. (2010) · Glia · doi:10.1002/glia.20973 · Cited by 108
“Leukocyte expression of CD36 has been reported to be low in patients with AD or mild cognitive impairment as well as in old AD mice (Hickman et al., 2008).”
BackgroundResultMicroglial mitophagy mitigates neuroinflammation in Alzheimer's disease
Lautrup, S., Lou, G., Aman, Y., Nilsen, H., Tao, J., & Fang, E. F. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.104469 · Cited by 105
“neuroinflammation, were shown to exhibit increased levels of pro-inflammatory cytokines including interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) coupled with a decrease of the anti-inflammatory cytokine interleukin-10 (IL-10), as previously reported (Heneka et al., 2013; Hickman et al., 2008).”
Brain injury, neuroinflammation and Alzheimer's disease
Breunig, J. J., Guillot‐Sestier, M., & Town, T. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00026 · Cited by 106
“Additionally, it has been extensively reported that aging microglia undergo structural deterioration and cellular senescence, which likely predicts poor Aβ clearance aptitude (Flanary and Streit, 2004; Fiala et al., 2005; Hickman et al., 2008; Njie et al., 2012).”
BackgroundHernandez, M. X., Jiang, S., Cole, T. A., Chu, S., Fonseca, M. I., Fang, M. J., Hohsfield, L. A., Torres, M. D., Green, K. N., Wetsel, R. A., et al. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0210-z · Cited by 104
Metadata
- Authors
- Hickman, S. E., Allison, E. K., & El Khoury, J.
- Affiliations
- Harvard University (US)
- ORCID
- Hickman, Suzanne E.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-08-13
- Volume
- 28
- Issue
- 33
- Pages
- 8354-8360
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2597474
- OpenAlex
- W2018708829
- Cited by
- 1,329
- References
- 28
- Citations by year
- 2026: 49 · 2025: 85 · 2024: 85 · 2023: 96 · 2022: 125 · 2021: 98 · 2020: 113 · 2019: 91 · 2018: 78 · 2017: 63 · 2016: 67 · 2015: 73 · 2014: 64 · 2013: 49 · 2012: 65
- FWCI
- 27.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dana Foundation
- National Institute of Neurological Disorders and Stroke (R01NS059005)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- Alzheimer's disease, microglia, amyloid-beta clearance, aging, scavenger receptor A, CD36, RAGE, neprilysin, MMP-9, inflammatory cytokines, TNF-α, IL-1β, neuroinflammation, anti-inflammatory therapy, neurodegeneration
- MeSH terms
- Aging, Alzheimer Disease, Animals, Mice, Transgenic, Signal Transduction, Amyloid beta-Peptides, Microglia, Mice
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