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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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In the citing paper
“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).”
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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×
“A, B, D, At 8 and 14 months of age, PS1-APP transgenic mice show significantly reduced expression of SRA (A), CD36 (B), and RAGE (D) compared with their WT littermates.”
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×
“This process is observed at the age of 8 months and appears to precede or parallel the increase in A levels observed in PS1-APP mice at that age (Jankowsky et al., 2001, 2004).”
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
Simard, A. R., Soulet, D., Gowing, G., Julien, J.-P., & Rivest, S. (2006) · Neuron · doi:10.1016/j.neuron.2006.01.022 · Cited by 1,265 · cited 2×
“…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×
“Indeed, early microglial accumulation appears to delay progression of AD-like pathology, and bone marrow-derived microglia may restrict plaque formation in transgenic mice (Simard et al., 2006; El Khoury et al., 2007).”
InfluentialSelf-citationMcGeer, P. L., Itagaki, S., Tago, H., & McGeer, E. G. (1987) · Neuroscience Letters · doi:10.1016/0304-3940(87)90696-3 · Cited by 836 · cited 1×
“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
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Items 401–500 of 1,003
Youn, K., Ho, C., & Jun, M. (2022) · Food Science and Human Wellness · doi:10.1016/j.fshw.2021.12.006 · Cited by 74
Why Did Tarenflurbil Fail in Alzheimer's Disease?
Imbimbo, B. P. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1092 · Cited by 75
“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 [28].”
Joshi, Y. B., & Praticò, D. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00436 · Cited by 75
“…effectively phagocytate high concentrations (or insoluble conformations) of it resulting in aberrantly activated microglia that associate with both Aβ plaques and neurofibrillary tangles (Hickman et al., 2008; Johnston et al., 2011; D’Andrea et al., 2004; Krabbe et al., 2013; Morales et al., 2013).”
BackgroundJungbauer, L. M., Yu, C., Laxton, K., & LaDu, M. J. (2009) · Journal of Molecular Recognition · doi:10.1002/jmr.948 · Cited by 74
“…(Paresce et al., 1996; Chung et al., 1999; Brazil et al., 2000; Li et al., 2000; El Khoury et al., 2007; Majumdar et al., 2007; Giunta et al., 2008; Hickman et al., 2008; Jiang et al., 2008; Parvathy et al., 2008) as well as Ab42 cellular binding, uptake and toxicity (Clifford et al., 2007;…”
BackgroundChowdhury, A. A., Gawali, N. B., Munshi, R., & Juvekar, A. R. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-0147-5 · Cited by 76
Repurposing the KCa3.1 inhibitor senicapoc for Alzheimer's disease
Jin, L., Lucente, J. D., Nguyen, H. M., Singh, V., Singh, L., Chavez, M., Bushong, T. R., Wulff, H., & Maezawa, I. (2019) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.754 · Cited by 77
Remembering your A, B, C's: Alzheimer's disease and ABCA1
Lewandowski, C. T., Laham, M. S., & Thatcher, G. R. J. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.01.011 · Cited by 76
Yin, P., Wang, X., Wang, S., Wei, Y., Feng, J., & Zhu, M. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00466 · Cited by 73
Innate Immunity in Alzheimer’s Disease: A Complex Affair
Guillot‐Sestier, M., & Town, T. (2013) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527311312050008 · Cited by 72
“Abbreviations used: APP, amyloid precursor protein; Cdk5, cyclin-dependent kinase 5; IDE, insulin degrading enzyme; IFN-γ, interferon-gamma; IL, interleukin; MHC II, major histocompatibility complex, class II; MIP-1α, macrophage inflammatory protein, type 1alpha; MMP9, matrix metalloprotease, type 9; NEP, neprilysin;…”
BackgroundAlzheimer’s Disease and Diabetes: Role of Diet, Microbiota and Inflammation in Preclinical Models
Carranza-Naval, M. J., Vargas-Soria, M., Hierro‐Bujalance, C., Baena‐Nieto, G., García-Alloza, M., Infante‐Garcia, C., & del Marco, À. (2021) · Biomolecules · doi:10.3390/biom11020262 · Cited by 77
“Thereby, microglia is chronically activated in the proximity of amyloid plaques and limits amyloid plaque growth [14] but, as the disease progresses, microglia fails to clear Aβ from brain parenchyma and ultimately contributes to the neurodegenerative process [13,15,16].”
BackgroundRAGE-TXNIP axis drives inflammation in Alzheimer’s by targeting Aβ to mitochondria in microglia
Sbai, O., Djelloul, M., Auletta, A., Ieraci, A., Vascotto, C., & Perrone, L. (2022) · Cell Death & Disease · doi:10.1038/s41419-022-04758-0 · Cited by 72
“When chronically activated, microglia become dysfunctional [5] and promotes neurodegeneration [6].”
BackgroundAlzheimer’s Disease and ncRNAs
Maoz, R., Garfinkel, B. P., & Soreq, H. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-53889-1_18 · Cited by 74
Multiple inflammatory profiles of microglia and altered neuroimages in APP/PS1 transgenic AD mice
Liu, L., Liu, Y., Li, N., Huang, R., Zheng, X., Huang, L., Hou, S.-X., & Yuan, Q. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.01.003 · Cited by 71
Targeting Microglia in Alzheimer’s Disease: Pathogenesis and Potential Therapeutic Strategies
Sun, Z., Zhang, X., So, K.-F., Jiang, W., & Chiu, K. (2024) · Biomolecules · doi:10.3390/biom14070833 · Cited by 71
“During the early stages of AD, activated microglia primarily exert protective effects by eliminating A β plaques through phagocytosis and the release of proteases, as well as engulfing dead cell debris [15]. en-gulfing dead cell debris [15].”
BackgroundKoronyo‐Hamaoui, M., Sheyn, J., Hayden, E. Y., Li, S., Fuchs, D.-T. S., Regis, G. C., Lopes, D. H. J., Black, K. L., Bernstein, K. E., Teplow, D. B., et al. (2019) · Brain · doi:10.1093/brain/awz364 · Cited by 75
“…pruning (Hong et al., 2016; Johnson and Stevens, 2018), while insufficiently clearing misfolded amyloid-b (Morgan et al., 2005; Simard et al., 2006; El Khoury et al., 2007; Hickman et al., 2008; Koronyo-Hamaoui et al., 2009; Yamanaka et al., 2012; Frenkel et al., 2013; Roussos et al., 2015).”
BackgroundAdetuyi, B. O., & Farombi, E. O. (2021) · Journal of Food Biochemistry · doi:10.1111/jfbc.13660 · Cited by 71
Gedam, M., Comerota, M. M., Propson, N. E., Chen, T., Jin, F., Wang, M. C., & Zheng, H. (2023) · Journal of Clinical Investigation · doi:10.1172/jci167501 · Cited by 74
“With the rescue of synapses and reduction in dystrophic neurites, we wanted to test the effect of C3aR on Phagocytosis, a major function of the microglia to maintain brain homeostasis, is compromised with age and in pathological conditions such as AD (52).”
Bhat, N. R. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06978.x · Cited by 71
“However, there is also the suggestion that resident microglia may be ill equipped in the latter capacity perhaps due to age and advanced disease state (Hickman et al. 2008; Njie et al. 2010).”
BackgroundKummer, M. P., Vogl, T., Axt, D., Griep, A., Vieira-Saecker, A. M. M., Jessen, F., Gelpí, E., Roth, J., & Heneka, M. T. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1504-12.2012 · Cited by 72
“The observed detrimental impact of long lasting A -induced inflammatory stimulation of microglia and the resulting deficits in A clearance is in agreement with this hypothesis (Hickman et al., 2008).”
ResultFrederiksen, H. R., Haukedal, H., & Freude, K. (2019) · BioMed Research International · doi:10.1155/2019/7420189 · Cited by 63
“The compromised Aβ clearance and persistent release of proinflammatory mediators in turn damage nearby neurons further promoting neurodegeneration, accelerating disease progression [20].”
BackgroundNeuroimmune contributions to Alzheimer’s disease: a focus on human data
Haage, V., & De Jager, P. L. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01637-0 · Cited by 74
Ikezu, S., & Ikezu, T. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00033 · Cited by 70
“…as CCL2, which are highly up-regulated in the LOAD brain (Xia and Hyman, 1999; Grammas and Ovase, 2001; Lue et al., 2001; Sun et al., 2003; Pola et al., 2004; Janelsins et al., 2005; Yamamoto et al., 2005; Galimberti et al., 2006; El Khoury et al., 2007; Hickman et al., 2008; Semple et al., 2010).”
BackgroundMcCarthy, R. C., Lu, D., Alkhateeb, A. A., Gardeck, A. M., Lee, C., & Wessling‐Resnick, M. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0484-z · Cited by 67
Cellular and Molecular Mediators of Neuroinflammation in Alzheimer Disease
Yang, S. (2019) · International Neurourology Journal · doi:10.5213/inj.1938184.092 · Cited by 72
“The continuous activation results in sustained signaling transduction by pro-inflammatory cytokines, leading to neuronal damage and resulting in the loss of phagocytosis activity by microglia and diminished breakdown of Aβ plaques [28,29].”
BackgroundWirz, K. T. S., Bossers, K., Stargardt, A., Kamphuis, W., Swaab, D. F., Hol, E. M., & Verhaagen, J. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.11.008 · Cited by 65
“In contrast to earlier reports (Hickman et al., 2008; Ruan et al., 2009), our data show that in APPswe/PS1dE9 mice well-known proinflammatory mediators (Il-1, Il-6, tumor necrosis factor a [Tnfa], interferon g, and Tgfß) were not significantly increased.”
Addressing Blood–Brain Barrier Impairment in Alzheimer’s Disease
Sharma, C., Woo, H., & Kim, S. R. (2022) · Biomedicines · doi:10.3390/biomedicines10040742 · Cited by 72
Yang, H. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17081041 · Cited by 78
“Nanoparticle delivery of mammalian target of rapamycin (mTOR) or NLRP3 reprogramming agents to microglia for phenotypic conversion could potentially work better with protein-clearance methods [86,129].”
Takamatsu, K., Ikeda, T., Haruta, M., Matsumura, K., Ogi, Y., Nakagata, N., Uchino, M., Ando, Y., Nishimura, Y., & Senju, S. (2014) · Stem Cell Research · doi:10.1016/j.scr.2014.10.001 · Cited by 69
Tribouillard‐Tanvier, D., Striebel, J. F., Peterson, K. E., & Chesebro, B. W. (2009) · Journal of Virology · doi:10.1128/jvi.01413-09 · Cited by 73
“Alternatively, activated glia may also contribute to progression of some CNS diseases including prion diseases (7, 23, 25, 27, 37, 53).”
BackgroundAlarmins and c-Jun N-Terminal Kinase (JNK) Signaling in Neuroinflammation
Anfinogenova, Y., Quinn, M. T., Schepetkin, I. A., & Atochin, D. N. (2020) · Cells · doi:10.3390/cells9112350 · Cited by 68
Microglial response to experimental periodontitis in a murine model of Alzheimer’s disease
Kantarcı, A., Tognoni, C. M., Yaghmoor, W., Marghalani, A. A., Stephens, D. N., Ahn, J.-Y., Carreras, I., & Dedeoglu, A. (2020) · Scientific Reports · doi:10.1038/s41598-020-75517-4 · Cited by 72
Müller cell degeneration and microglial dysfunction in the Alzheimer’s retina
Xu, Q., Boerkoel, P., Hirsch‐Reinshagen, V., Mackenzie, I. R., Hsiung, G. R., Charm, G., To, E., Liu, A., Schwab, K. D., Jiang, K., et al. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01448-y · Cited by 68
“These data are consistent with the proliferation of dysfunctional microglia, with the exhaustion of healthy microglial cells, observed in the brain [15, 28, 45, 55].”
ResultMicroglial toll-like receptors and Alzheimer’s disease
Su, F., Bai, F., Zhou, H., & Zhang, Z. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.10.010 · Cited by 69
“vated microglia clear amyloid plaques (Hickman et al., 2008; Maier et al., 2008; Tahara et al., 2006), which are believed to be”
InfluentialCui, Y., Wang, Y., Zhao, D., Feng, X., Zhang, L., & Liu, C. (2018) · Cell Biology International · doi:10.1002/cbin.11060 · Cited by 68
“One previous study showed that the expression of Abdegrading enzyme and Ab-binding scavenger receptor in microglia of AD mice are decreased (Hickman et al., 2008).”
BackgroundMudimela, S., Vishwanath, N. K., Pillai, A., Morales, R., Marrelli, S. P., Barichello, T., & Giridharan, V. V. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.08.002 · Cited by 71
Molecular Mechanisms Underlying Neuroinflammation Elicited by Occupational Injuries and Toxicants
Pathak, D., & Sriram, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032272 · Cited by 72
Madhu, L. N., Kodali, M., Upadhya, R., Rao, S., Somayaji, Y., Attaluri, S., Shuai, B., Kirmani, M., Gupta, S., Maness, N., et al. (2024) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12519 · Cited by 69
“In both AD models and patients, A β plaques increase progressively and are surrounded by activated microglia with DAM genes signature and an impaired ability for phagocytosis and A β clearance (Hickman et al., 2008; Meyer-Luehmann et al., 2008).”
BackgroundKim, J. A., Ha, S., Shin, K. Y., Kim, S., Lee, K. J., Chong, Y. H., Chang, K.-A., & Suh, Y.-H. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.138 · Cited by 70
Gupta, N., Shyamasundar, S., Patnala, R., Karthikeyan, A., Arumugam, T. V., Ling, E., & Dheen, S. T. (2018) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2018.1515917 · Cited by 67
Microglia: Friend and foe in tauopathy
Odfalk, K. F., Bieniek, K. F., & Hopp, S. C. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102306 · Cited by 60
Astrocytes and microglia in neurodegenerative diseases: Lessons from human in vitro models
Franklin, H., Clarke, B. E., & Patani, R. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101973 · Cited by 66
“However, evidence points to a combination of dysfunctional Aβ-clearing mechanisms (Hickman et al., 2008) and Aβ-induced activation of proinflammatory processes through upregulated secretion of cytokines and neurotoxins (Guillot-Sestier and Town, 2013).”
BackgroundYang, Y., He, Z., Xing, Z., Zuo, Z., Yuan, L., Wu, Y., Jiang, M. H., Qi, F., & Yao, Z. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01741-4 · Cited by 67
“Evidence suggests that the ability of microglial activation surrounding Aβ plaques to protect against the occurrence of AD may decrease with age and disease progression because of impaired microglial function [28, 29].”
Xie, J., Gorlé, N., Vandendriessche, C., Imschoot, G. V., Wonterghem, E. V., Cauwenberghe, C. V., Parthoens, E., Hamme, E. V., Lippens, S., Hoecke, L. V., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01253-z · Cited by 69
Neuroinflammatory Biomarkers in Alzheimer’s Disease: From Pathophysiology to Clinical Implications
Roveta, F., Bonino, L., Piella, E. M., Rainero, I., & Rubino, E. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252211941 · Cited by 80
“Astrocytes also play a critical role in the response to A β plaques, surrounding them to isolate the pathological deposits from healthy brain tissue [31,32].”
Zhang, X., Wang, B., O'Callaghan, P. W., Hjertström, E., Jia, J., Gong, F., Zcharia, E., Nilsson, L. N. G., Lannfelt, L., Vlodavsky, I., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-0997-1 · Cited by 67
“Such macrophages, recruited in response to cerebral injection of pre-aggregated Ab, are thought to be better Ab phagocytes than brain resident immune cells [10, 12, 24, 51], and poor infiltration of blood-borne macrophages may therefore contribute to Ab accumulation [57].”
BackgroundMicroglial KCa3.1 Channels as a Potential Therapeutic Target for Alzheimer’s Disease
Maezawa, I., Jenkins, D. P., Jin, B. E., & Wulff, H. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/868972 · Cited by 64
“and by phagocytosing Aβ and debris from degenerated neurons [14, 23].”
BackgroundHHV-6A infection induces amyloid-beta expression and activation of microglial cells
Bortolotti, D., Gentili, V., Rotola, A., Caselli, E., & Rizzo, R. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0552-6 · Cited by 66
“On the one hand, Aβ neuritic plaques are surrounded by activated microglial cells that could contribute to Aβ phagocytosis and/or compaction [37, 38].”
BackgroundModulation of β-Amyloid Fibril Formation in Alzheimer’s Disease by Microglia and Infection
Brown, M. R., Radford, S. E., & Hewitt, E. W. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.609073 · Cited by 67
“MMP-9 was also found to degrade compact Aβ amyloid plaques in brain sections from AD model (APP/PS1) mice (Yan et al., 2006).”
BackgroundInfluentialHe, X., Xu, J., Li, G., Li, M., Li, L., Pei, Z., Zhang, L., & Hu, X. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-03072-x · Cited by 64
Psychedelic‐inspired approaches for treating neurodegenerative disorders
Saeger, H. N., & Olson, D. E. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15544 · Cited by 72
“These dystrophic microglia, which are thought to arise from chronic exposure to Aβ species, contribute to disease progression by releasing pro- inflammatory factors why failing to phagocytose and degrade Aβ species (Angelova et al., 2019; Hickman et al., 2008; Ritzel et al., 2019).”
BackgroundJi, Y., Chen, X., Wang, Z., Meek, C. J., McLean, J. L., Yang, Y., Yuan, C., Rochet, J., Liu, F., & Xu, R. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03041-w · Cited by 74
“Overall, our proteomics data indicate that the AD neuroimmune organoids successfully replicate the major disrupted pathways and molecular signatures of AD observed in patients, corroborating our fi ndings on cellular dysfunction in these organoids.”
Functions of the CB1 and CB2 Receptors in Neuroprotection at the Level of the Blood–Brain Barrier
Vendel, E., & de Lange, E. C. M. (2014) · NeuroMolecular Medicine · doi:10.1007/s12017-014-8314-x · Cited by 67
“2002), but as AD progresses, microglia continue to produce pro-inflammatory cytokines and lose their ability to clear AB (Hickman et al. 2008).”
BackgroundWoodling, N. S., & Andreasson, K. I. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6b00016 · Cited by 62
Fox, B. M., Beck, H. P., Roveto, P. M., Kayser, F., Cheng, Q., Dou, H., Williamson, T. L., Treanor, J. J. S., Liu, H., Jin, L., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00567 · Cited by 64
Exploring glia to better understand Alzheimer’s disease
Kim, Y. S., Jung, H. M., & Yoon, B. (2018) · Animal Cells and Systems · doi:10.1080/19768354.2018.1508498 · Cited by 68
“turn, are either suppressed through apoptosis or continue to activate other microglial cells (Block et al. 2007; Hickman et al. 2008).”
BackgroundMicroglia dynamics in adolescent traumatic brain injury
Eyolfson, E., Khan, A. C., Mychasiuk, R., & Lohman, A. W. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01994-z · Cited by 68
“Dysregulation of microglial function has been implicated in a number of neurological disorders and pathologies including obsessive compulsive disorder [133], AD [134], PD [135], chronic traumatic encephalopathy (CTE) [136], and brain infections [137].”
BackgroundTargeting Microglia-Synapse Interactions in Alzheimer’s Disease
Piccioni, G., Mango, D., Saidi, A., Corbo, M., & Nisticò, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052342 · Cited by 64
“Therefore, during early stage of AD, clustered microglia has protective effects since it eliminates Aβ plaques, dying or dead cells by its phagocytic activity or by releasing proteases (insulin degrading enzyme, neprilysin, matrix metalloproteinase 9 and plasminogen) [61].”
BackgroundCo-aggregation with Apolipoprotein E modulates the function of Amyloid-β in Alzheimer’s disease
Xia, Z., Prescott, E. E., Urbanek, A., Wareing, H. E., King, M. C., Olerinyova, A., Dakin, H., Leah, T., Barnes, K. A., Matuszyk, M. M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49028-z · Cited by 67
“Human microglia and astrocytes take up soluble and insoluble A β aggregates 49,50 , and dysfunction of microglia and astrocytes is implicated in AD 51,52 .”
BackgroundRaj, D. D. A., Moser, J., van der Pol, S. M. A., van Os, R. P., Holtman, I. R., Brouwer, N., Oeseburg, H., Schaafsma, W., Wesseling, E. M., den Dunnen, W. F. A., et al. (2015) · Aging Cell · doi:10.1111/acel.12370 · Cited by 65
The role of the immune system in driving neuroinflammation
Ní Chasaide, C., & Lynch, M. A. (2020) · Brain and Neuroscience Advances · doi:10.1177/2398212819901082 · Cited by 72
“It is proposed that microglia may clear Aβ in early disease, but switch to an inflammatory and less phagocytic phenotype as disease progresses (Hickman et al., 2008).”
BackgroundWang, M., Tang, G., Zhou, C., Guo, H., Hu, Z., Hu, Q., & Li, G. (2023) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2023.110387 · Cited by 62
Wu, J., Bie, B., Yang, H., Xu, J. J., Brown, D. L., & Naguib, M. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.06.003 · Cited by 62
“However, as AD progresses, microglia lose their Ab-clearing capabilities and continue to produce proinflammatory cytokines such as IL-1b (Hickman et al., 2008).”
BackgroundHoeijmakers, L., Lesuis, S. L., Krugers, H. J., Lucassen, P. J., & Kőrösi, A. (2018) · Neurobiology of Stress · doi:10.1016/j.ynstr.2018.02.003 · Cited by 66
Cornejo, F., Vruwink, M., Metz, C., Muñoz, P., Salgado, N., Poblete, J., Andrés, M. E., Eugenín, J., & von Bernhardi, R. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2017.12.007 · Cited by 59
Function of exosomes in neurological disorders and brain tumors
Xiao, L., Hareendran, S., & Loh, Y. P. (2021) · Extracellular Vesicles and Circulating Nucleic Acids · doi:10.20517/evcna.2021.04 · Cited by 62
Estfanous, S. Z. K., Daily, K. P., Eltobgy, M. M., Deems, N. P., Anne, M. N. K., Krause, K., Badr, A., Hamilton, K., Carafice, C., Hegazi, A., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.705581 · Cited by 64
“org 10 dysfunctional over the course of AD and fail to clear Ab, and instead they release toxic neuro-inflammatory products (10).”
BackgroundMethodInfluentialXu, Y., Au, N. P. B., & Ma, C. H. E. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.896852 · Cited by 68
Immunotherapies for Alzheimer’s Disease—A Review
Valiukas, Z., Ephraim, R., Tangalakis, K., Davidson, M., Apostolopoulos, V., & Feehan, J. (2022) · Vaccines · doi:10.3390/vaccines10091527 · Cited by 70
“Interleukin (IL) 1α plays a significant role in overexpression of APP, as well as being highly expressed in an AD brain compared to a healthy brain [57] which can create a loop of IL-1 secretion and APP synthesis.”
BackgroundMishra, P., Silva, A., Sharma, J., Nguyen, J., Pizzo, D. P., Hinz, D., Sahoo, D., & Cherqui, S. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112956 · Cited by 64
“Finally, comprehensive understanding of the mechanism underlying the behavioral rescue in AD by WT HSPCs remains to be discovered.”
Al-Khazaleh, A. K., Zhou, X., Bhuyan, D. J., Münch, G. W., Al-Dalabeeh, E. A., Jaye, K. M., & Chang, D. (2024) · Molecules · doi:10.3390/molecules29020410 · Cited by 66
Inflammation and Microglia Actions in Alzheimer’s Disease
Combs, C. K. (2009) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9165-3 · Cited by 62
Crocetin attenuates inflammation and amyloid-β accumulation in APPsw transgenic mice
Zhang, J., Wang, Y., Dong, X., & Liu, J. (2018) · Immunity & Ageing · doi:10.1186/s12979-018-0132-9 · Cited by 61
“Moreover, activation of microglia may lead to accumulation of Aβ and formation of neurofibrillary tangles [6, 7].”
Landlinger, C., Oberleitner, L., Gruber, P., Noiges, B., Yatsyk, K., Santic, R., Mandler, M., & Staffler, G. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0369-6 · Cited by 60
“The complement component C5a, however, is supposed to play a detrimental role in neurodegenerative diseases by persistent microglia activation resulting in excessive release of microglial inflammatory mediators, which enhance Aβ deposition and neuroinflammation [40, 42, 43].”
BackgroundStress Granules Modulate SYK to Cause Microglial Cell Dysfunction in Alzheimer's Disease
Ghosh, S., & Geahlen, R. L. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.09.053 · Cited by 62
“MG in aged and AD brain fail to clear Aβ plaques, but display an activated, pro-inflammatory phenotype (Krabbe et al., 2013; Hickman et al., 2008; Mosher and Wyss-Coray, 2014).”
BackgroundMarples, B., McGee, M. C., Callan, S. P., Bowen, S. E., Thibodeau, B. J., Michael, D. B., Wilson, G. D., Maddens, M. E., Fontanesi, J., & Martinez, A. A. (2015) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2015.10.019 · Cited by 60
Age-Dependent Changes in the Activation and Regulation of Microglia
Cornejo, F., & Rommy von Bernhardi, M. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-40764-7_10 · Cited by 61
Chemokines in Alzheimer’s Disease: New Insights Into Prokineticins, Chemokine-Like Proteins
Zuena, A. R., Casolini, P., Lattanzi, R., & Maftei, D. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00622 · Cited by 61
“Several studies from post-mortem brains of AD patients and AD animal models have revealed a co-localization of reactive glial cells with senile plaques and neurofibrillary tangles (Parachikova et al., 2007; Hickman et al., 2008; Lopez-Gonzalez et al., 2015).”
BackgroundLee, J., Kim, H., Kim, J., Yook, T. H., Kim, K. H., Lee, J. Y., & Yang, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031324 · Cited by 61
“Furthermore, abnormal microglia‐specific NLRP3 activation induced chronic neuro‐inflammation in the pathological process of AD, resulting in microglia Aβ phagocytic dysfunction, peripheral nerve cell damage, and severe pathological damage [23].”
BackgroundWang, Y.-B., Li, X., Bing, Y., Zhang, Q., Fei-Tong, J., Minghong, W., Xiangxiang, Z., Le, K., Li, Y., Ping, S., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04765-1 · Cited by 60
“However, microglia still produce proinflammatory cytokines [49].”
Larochelle, A., Bellavance, M., Michaud, J.-P., & Rivest, S. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.09.017 · Cited by 60
Inflammatory Risk Factors and Pathologies Associated with Alzheimers Disease
Sastre, M., Richardson, J. C., Gentleman, S., & Brooks, D. J. (2011) · Current Alzheimer Research · doi:10.2174/156720511795256062 · Cited by 59
Microglial Responses to Brain Injury and Disease: Functional Diversity and New Opportunities
Lyu, J., Jiang, X., Leak, R. K., Shi, Y., Hu, X., & Chen, J. (2020) · Translational Stroke Research · doi:10.1007/s12975-020-00857-2 · Cited by 63
“Aged microglia display a decrease in the capacity to degrade cellular debris such asβ-amyloid, as suggested by reduced expression of β-amyloid degrading enzymes, which may exacerbate neurological deficits in neurodegenerative diseases [187, 188].”
BackgroundMyeloid Cells in Alzheimer's Disease: Culprits, Victims or Innocent Bystanders?
Meyer‐Luehmann, M., & Prinz, M. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.08.011 · Cited by 58
Fernando, K., & Wijayasinghe, Y. S. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.746631 · Cited by 57
“As the disease progresses, a decline in microglial phagocytic efficiency has been observed due to decreased expression of the Aβ-binding SR-A1, CD36, and RAGE, as well as the enzymes that degrade Aβ (Hickman et al., 2008).”
BackgroundXia, Y., Wu, Q., Mak, S., Liu, E. Y. L., Zheng, B. Z.-Y., Dong, T. T.-X., Pi, R., & Tsim, K. W. K. (2022) · The FASEB Journal · doi:10.1096/fj.202101302rr · Cited by 61
Takata, K., Takada, T., Ito, A., Asai, M., Tawa, M., Saito, Y., Ashihara, E., Tomimoto, H., Kitamura, Y., & Shimohama, S. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/685739 · Cited by 60
“However, it has been reported that microglial dystrophy occurs in aging human brains [26], and the age-related disability of microglial Aβ phagocytosis has been demonstrated experimentally [27].”
BackgroundXie, Z., Liu, Z., Zhang, X., Yang, H., Wei, L., Wang, Y., Xu, S., Sun, L., Lai, C., Bi, J., et al. (2015) · Clinical and Experimental Medicine · doi:10.1007/s10238-015-0375-0 · Cited by 60
“These pro-inflammatory cytokines can act in an autocrine fashion and promote Ab production and reduced Ab clearance [33].”
BackgroundMicroglial Priming in Infections and Its Risk to Neurodegenerative Diseases
Lima, M. N., Barbosa‐Silva, M. C., & Maron‐Gutierrez, T. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.878987 · Cited by 66
Nelson, L., Gard, P., & Tabet, N. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140024 · Cited by 59
“Mouse models of familial AD have shown microglia physiology changes with age, becoming less efficient at clearing amyloid deposits, but remaining able to produce proinflammatory molecules [68].”
BackgroundShin, J., Lee, J. K., Lee, J. E., Min, W., Schuchman, E. H., Jin, H. K., & Bae, J. (2011) · Stem Cells · doi:10.1002/stem.659 · Cited by 56
γ‐Secretase component presenilin is important for microglia β‐amyloid clearance
Farfara, D., Trudler, D., Segev‐Amzaleg, N., Galron, R., Stein, R., & Frenkel, D. (2010) · Annals of Neurology · doi:10.1002/ana.22191 · Cited by 57
“Isolation of Adult Microglia Adult microglia were isolated from 12-week-old WT or PS2 / mice brains and cultured as described.(18) Measurement of Nitrite Levels”
MethodShamim, D., & Laskowski, M. C. (2017) · Journal of Central Nervous System Disease · doi:10.1177/1179573517722512 · Cited by 56
Microglial Extracellular Vesicles as Vehicles for Neurodegeneration Spreading
Aires, I. D., Ribeiro‐Rodrigues, T., Boia, R., Ferreira-Rodrigues, M., Girão, H., Ambrósio, A. F., & Santiago, A. R. (2021) · Biomolecules · doi:10.3390/biom11060770 · Cited by 57
“Although the initial activation of microglia is beneficial for clearing toxic Aβ from the brain in AD, over time the chronic stimulation of microglia by Aβ may also be deleterious and lead to prolonged inflammation, excessive Aβ deposition and acceleration of the neurodegenerative process [25].”
BackgroundJiang, M., Zhang, X., Yan, X., Mizutani, S., Kashiwazaki, H., Ni, J., & Wu, Z. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.08.213 · Cited by 61
Inflamma-MicroRNAs in Alzheimer’s Disease: From Disease Pathogenesis to Therapeutic Potentials
Liang, Y., & Wang, L. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.785433 · Cited by 56
Gomes, P., Tzouanou, F., Skolariki, K., Vamvaka-Iakovou, A., Nogueras‐Ortiz, C. J., Tsirtsaki, K., Waites, C. L., Vlamos, P., Sousa, N., Costa‐Silva, B., et al. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114183 · Cited by 60
“…is beneficial for clearing toxic A β from the AD brain, over time, the chronic stimulation of microglia by A β may also be deleterious, leading to prolonged inflammation, excessive A β deposition, and acceleration of the neurodegenerative process (Sala Frigerio et al., 2019; Hickman et al., 2008).”
Neurodegeneration as an RNA disorder
Johnson, R., Noble, W. J., Tartaglia, G. G., & Buckley, N. J. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.09.006 · Cited by 56
“also results from increased pro-inflammatory cytokine production by microglia in models of AD (Hickman et al., 2008).”
BackgroundInfluentialHao, W., Liu, Y., Liu, S., Walter, S., Grimm, M. O. W., Kiliaan, A. J., Penke, B., Hartmann, T., Rübe, C. E., Menger, M. D., et al. (2010) · Brain · doi:10.1093/brain/awq325 · Cited by 54
“Previous studies suggest that inflammatory activation inhibits phagocytosis in mononuclear phagocytes (Koenigsknecht-Talboo and Landreth, 2005; Townsend et al., 2005; Zelcer et al., 2007; Hickman et al., 2008).”
BackgroundChowdhury, A. A., Gawali, N. B., Shinde, P., Munshi, R., & Juvekar, A. R. (2018) · Cytokine · doi:10.1016/j.cyto.2018.04.018 · Cited by 57
Elongator mutation in mice induces neurodegeneration and ataxia-like behavior
Kojic, M., Gaik, M., Kiska, B., Salerno-Kochan, A., Hunt, S., Tedoldi, A., Mureev, S., Jones, A., Whittle, B., Genovesi, L. A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05765-6 · Cited by 56
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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