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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Microglial phagocytic capacity declines with aging, chronic exposure to Aβ, and during sustained inflammation in the AD brain.
“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]
The Discussion reports declining Aβ-clearing ability as PS1-APP mice age and AD-like pathology progresses. The Results show reduced Aβ uptake after TNFα treatment and increased inflammatory cytokines in older mice with continued Aβ deposition. The paper does not establish chronic Aβ exposure as a separate cause of declining phagocytosis or demonstrate the claimed decline in human AD brains; its direct evidence is from mice and cultured mouse microglia. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAs AD progresses, microglia acquire a chronically activated phenotype through unremitting stimulation by cytokines and Aβ itself, which compromises their clearance function.
“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
The Discussion reports that microglia in aging AD-model mice continue producing pro-inflammatory cytokines while losing Aβ-clearing capacity; it also links Aβ-induced inflammation to reduced expression of clearance receptors. The paper does not establish that unremitting stimulation by both cytokines and Aβ causes a chronically activated phenotype, and it frames some cytokine effects as possible mechanisms rather than demonstrated causes. Page numbers were not supplied for these passages. (LLM, conf=0.82)
Experimental — accuracy not yet measuredProgression of Alzheimer's disease is associated with reduced Aβ-clearing pathways resulting in Aβ accumulation.
“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]
The Discussion reports that, as AD-like pathology progresses in PS1-APP mice, microglia show reduced Aβ uptake and degradation alongside increased Aβ accumulation. The citing sentence states this as a general feature of Alzheimer's disease progression, whereas the paper's direct evidence comes from a mouse model. (LLM, conf=0.84)
Experimental — accuracy not yet measuredProgression 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.
“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]
The Results section reports reduced expression of Aβ-degrading enzymes in microglia from older PS1-APP mice, and the Discussion links reduced enzyme expression to reduced Aβ degradation and increased accumulation. The paper does not establish the same enzyme-expression change in humans, so the claim’s extension to human Alzheimer’s disease is unsupported by this source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThis impairment has been shown to correlate with increased production of proinflammatory cytokines and overwhelming accumulation of Aβ plaques in the AD brain.
“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]
The Results report increased proinflammatory cytokine expression in older PS1-APP mice and florid Aβ plaques in their brains; the Discussion links impaired microglial Aβ clearance to increased Aβ accumulation. The evidence comes from a mouse model of AD, however, and does not establish this correlation in the human AD brain. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Microglial function may be adversely affected by Aβ, particularly as a result of chronic exposure to pro-inflammatory cytokines, resulting in increased Aβ accumulation.
“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 <i>INPP5D</i> limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [40]
The expression of CD36 parallels the ability of microglia to perform Aβ clearance.
“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]
Increased pro-inflammatory gene expression in response to accumulating Aβ in older AD mice leads to decreased microglial Aβ clearance receptors or Aβ-degrading enzymes, thereby promoting further Aβ accumulation.
“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 ability of microglia to remove Aβ declines over time.
“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]
Progression of amyloid pathology correlates with impaired capacity of microglia to phagocytose Aβ.
“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]
Loss of microglial phagocytic capacity leads to further Aβ accumulation and aggregation, accelerating AD progression.
“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]
Expression of IDE in microglia from PS1-APP mice decreases with age and progression of AD-like pathology.
“We have previously shown that expression of IDE in microglia from PS1-APP mice decreases with age and progression of AD-like pathology (5).”
Constitutive deletion of miR155, which should increase SHIP1, led to an increase in amyloid plaques.
“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 <i>INPP5D</i> limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [40]
The Methods section lists the genes measured, and the Results and Discussion describe age-related defects in amyloid clearance in PS1-APP mice. Searches for miR155, Inpp5d, SHIP1, and constitutive deletion found no passage addressing whether miR155 deletion increases amyloid plaques. The paper’s discussion of amyloid accumulation does not establish that specific claim. (LLM, conf=0.77)
Experimental — accuracy not yet measuredInpp5d was identified as a target of miR155.
“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 <i>INPP5D</i> limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [40]
The Materials and Methods section (Quantitative Real Time PCR; page unavailable) lists the genes assayed but not Inpp5d or miR-155. Searches for Inpp5d, miR-155 and SHIP1 found no passage identifying Inpp5d as a miR-155 target in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredAged glial cells respond less efficiently to antigens, including amyloid-β and α-synuclein, and have reduced phagocytic and antiinflammatory capacity.
“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]
AD is accompanied by activation of microglia and astrocytes that affects clearance and production of Aβ, development and propagation of tau pathology, exacerbates neurodegeneration, and influences disease progression and severity.
“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]
Microglia from Aβ-mice have reduced expression of Aβ-phagocytic receptors and Aβ-degrading enzymes while retaining proinflammatory cytokine production.
“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 response to stimuli, microglia can initiate neuroinflammation with cytokines such as TNF and IL-1 and possibly Ccl2, recruiting cells to clear injurious agents and maintain brain homeostasis.
“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]
Aβ clearance involves microglial phagocytosis and endocytosis via scavenger receptors and extracellular degradation by Aβ-degrading enzymes.
“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]
Aβ clearance by microglia in AD may be ineffective despite phagocytic uptake.
“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 Alzheimer's disease, microglia cluster around beta-amyloid plaques, indicating an inability to clear beta-amyloid.
“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
Pro-inflammatory microglia are closely associated with protein aggregate pathologies characteristic of most dementias.
“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 Alzheimer's disease (AD), microglia surround amyloid plaques and respond to amyloid-β with a pro-inflammatory phenotype characterised by cytokine expression (IL1β, IL6, TNFα) that may initially limit amyloidosis but likely becomes overzealous and neurotoxic.
“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]
PS1-APP mice (a model of Alzheimer's Disease) show an age-dependent reduction in receptors and enzymes involved in beta amyloid degradation, although still maintaining elevated levels of cytokine.
“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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Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226 · see citing works
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Inflammation in obesity, diabetes, and related disorders
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TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer’s Disease Model
Wang, Y., Cella, M., Mallinson, K., Ulrich, J. D., Young, K. L., Robinette, M. L., Gilfillan, S., Krishnan, G. M., Sudhakar, S., Zinselmeyer, B. H., et al. (2015) · Cell · doi:10.1016/j.cell.2015.01.049 · Cited by 1,736 · see citing works
“At late stages of AD, microglia may paradoxically contribute to the disease by releasing pro-inflammatory cytokines in response to Aβ deposition (El Khoury et al., 2007; Hickman et al., 2008).”
Neuroinflammation and M2 Microglia: The Good, the Bad, and the Inflamed
Cherry, J. D., Olschowka, J. A., & O’Banion, M. K. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-98 · Cited by 1,748 · see citing works
“Correspondingly, in older, non-diseased mice there is downregulation of receptors associated with Aβ engulfment, such as scavenger receptor A and the Aβ degradation enzymes Nep, IDE, and MMP-9 [134].”
BackgroundMicroglia in neurodegeneration
Hickman, S., Izzy, S., Sen, P., Morsett, L., & El Khoury, J. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0242-x · Cited by 1,710 · see citing works
Self-citationThe microglial sensome revealed by direct RNA sequencing
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Self-citation<p>Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics</p>
Tiwari, S., Atluri, V., Kaushik, A., Yndart, A., & Nair, M. (2019) · International Journal of Nanomedicine · doi:10.2147/ijn.s200490 · Cited by 1,308 · see citing works
“However, in severe cases of AD, microglial clearance of Aβ is inefficient, due to increased localized cytokine concentrations, which downregulate the expression of Aβphagocytosis receptors and decrease Aβ clearance.(54) One of the factors behind compromised AD clearance by”
BackgroundiPSC-derived human microglia-like cells to study neurological diseases
Abud, E. M., Ramirez, R. N., Martinez, E. S., Healy, L. M., Nguyen, C. H. H., Newman, S. A., Yeromin, A. V., Scarfone, V. M., Marsh, S. E., Fimbres, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.03.042 · Cited by 1,154 · see citing works
“In AD, microglia cluster around beta-amyloid plaques highlighting their inability to clear beta-amyloid (Hickman et al., 2008, Liu et al., 2010).”
Microglia development and function
Nayak, D., Roth, T. L., & McGavern, D. B. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120240 · Cited by 1,154 · see citing works
Zhang, J., Zhang, Y., Wang, J., Xia, Y., Zhang, J., & Chen, L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01911-3 · Cited by 1,138 · see citing works
“174 ,175 A β also causes the formation and activation of the NLRP3 in fl ammasome within microglia, which releases ASC specks that bind rapidly to A β in promoting A β aggregates and the spread of A β pathology.”
BackgroundSimpson, D. S. A., & Oliver, P. L. (2020) · Antioxidants · doi:10.3390/antiox9080743 · Cited by 1,044 · see citing works
“Expression of amyloid-scavenging receptors (such as CD36) and amyloid-degrading enzymes decrease as aberrant inflammatory regulation ensues in AD [13].”
BackgroundOverview of General and Discriminating Markers of Differential Microglia Phenotypes
Jurga, A. M., Paleczna, M., & Kuter, K. Z. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00198 · Cited by 1,000 · see citing works
“Another important microglial multimeric complex protein is ferritin, which is responsible for iron storage and its homeostasis and is upregulated due to microglia activation (Holland et al., 2018).”
BackgroundInfluentialAmyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future
Zhang, Y., Chen, H., Li, R., Sterling, K., & Song, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01484-7 · Cited by 988 · see citing works
“In contrast, their capacity of proinflammatory cytokine production is unaffected, contributing to an exacerbation of AD pathology including Aβ accumulation and neuronal damage.(170,171) To compensate the impaired clearance of Aβ, peripheral macrophages are recruited to the brain in an effort to clear Aβ plaques, which…”
BackgroundSpangenberg, E., Severson, P. L., Hohsfield, L. A., Crapser, J., Zhang, J., Burton, E. A., Zhang, Y., Spevak, W., Lin, J., Phan, N. Y., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11674-z · Cited by 939 · see citing works
Neurovascular mechanisms and blood–brain barrier disorder in Alzheimer’s disease
Bell, R. D., & Zloković, B. V. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0522-3 · Cited by 855 · see citing works
“However, as the disease progresses the microglial activation may lead to inflammation, reduced Ab clearance and severe neurodegeneration [40].”
BackgroundPan, R.-Y., He, L., Zhang, J., Liu, X., Liao, Y., Gao, J., Liao, Y., Yan, Y., Li, Q., Zhou, X., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.02.013 · Cited by 862 · see citing works
Review: microglia of the aged brain: primed to be activated and resistant to regulation
Norden, D. M., & Godbout, J. P. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2012.01306.x · Cited by 792 · see citing works
The blood-brain barrier in Alzheimer’s disease
Zenaro, E., Piacentino, G., & Constantin, G. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.07.007 · Cited by 767 · see citing works
“…activation of microglia is accompanied by diminished phagocytosis and the more abundant secretion of pro-in fl ammatory cytokines, leading to the accumulation of A β and the ampli fi cation of neuroin fl ammation (El Khoury et al., 2007; Hickman et al., 2008; Krabbe et al., 2013; Heneka et al., 2015).”
Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques
Condello, C., Yuan, P., Schain, A., & Grutzendler, J. (2015) · Nature Communications · doi:10.1038/ncomms7176 · Cited by 718 · see citing works
Therapeutics of Alzheimer's disease: Past, present and future
Anand, R., Gill, K. D., & Mahdi, A. A. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.07.004 · Cited by 748 · see citing works
The role of microglia in amyloid clearance from the AD brain
Lee, C. Y. D., & Landreth, G. E. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0433-4 · Cited by 701 · see citing works
“reported that the levels of IDE, NEP and MMP9 were dramatically reduced in older mice with the concomitant upregulation of proinflammatory cytokines (Hickman et al. 2008).”
BackgroundInfluentialChiu, I. M., Morimoto, E. T. A., Goodarzi, H., Liao, J. T., O’Keeffe, S., Phatnani, H. P., Muratet, M., Carroll, M. C., Levy, S., Tavazoie, S., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.06.018 · Cited by 651 · see citing works
“Microglia were purified by sequential Percoll gradient centrifugation andmagnetic bead isolation (Figures 1A and S1B), in a procedure modified from previous protocols (Cardona et al., 2006a; Hickman et al., 2008).”
Microglial dysfunction in brain aging and Alzheimer's disease
Mosher, K. I., & Wyss-Coray, T. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.01.008 · Cited by 618 · see citing works
Deane, R., Singh, I., Sagare, A. P., Bell, R. D., Ross, N. T., LaRue, B., Love, R., Perry, S., Paquette, N., Deane, R. J., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci58642 · Cited by 619 · see citing works
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“Previously published transcriptomes from pure microglia, brain tissue, and cultured and stimulated macrophages were included in our analysis, for detailed platform and, experimental design information see Additional file 1: Table S1 [15,24-28].”
MethodPhysical exercise in the prevention and treatment of Alzheimer's disease
la Rosa, A. D., González, G. O., Arc‐Chagnaud, C., Millán-Domingo, F., Salvador‐Pascual, A., García-Lucerga, C., Blasco-Lafarga, C., García-Domínguez, E., Carretero, A., Correas, Á. G., et al. (2020) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2020.01.004 · Cited by 617 · see citing works
“16 During advanced stages of the disease there is a prolonged stimulation of the immune response caused by Ab, which leads to a decrease in the efficiency of the microglia to degrade it.(17) In turn, this leads to the release of several proinflammatory products, such as cytokines, reactive oxygen, and nitrogen species…”
BackgroundImmune activation in brain aging and neurodegeneration: too much or too little?
Lucin, K. M., & Wyss-Coray, T. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.039 · Cited by 679 · see citing works
“In a mouse model of AD, old PS1-APP mice have a 2-to 5-fold decrease in Ab-binding scavenger receptors and Ab-degrading enzymes, despite increases in proinflammatory cytokines (Hickman et al., 2008).”
BackgroundTraumatic brain injury and amyloid-β pathology: a link to Alzheimer's disease?
Johnson, V. E., Stewart, W., & Smith, D. H. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2808 · Cited by 587 · see citing works
“Interestingly, microglia also appear to utilize neprilysin to process A&beta”
BackgroundJanus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis
Sierra, A., Abiega, O., Shahraz, A., & Neumann, H. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00006 · Cited by 574 · see citing works
“…decreased expression of phagocytic genes (SRA, CD36, RAGE, etc.) and increased expression of pro-inflammatory cytokines (TNFα, IL-1β), compared with age-matched wild type mice (Hickman et al., 2008), but both findings cannot explain the failure of microglia to sufficiently clear Aβ plaque in vivo.”
BackgroundMicroglia, neuroinflammation, and beta-amyloid protein in Alzheimer’s disease
Cai, Z., Hussain, M. D., & Yan, L.-J. (2014) · International Journal of Neuroscience · doi:10.3109/00207454.2013.833510 · Cited by 583 · see citing works
Microglial cell dysregulation in brain aging and neurodegeneration
von Bernhardi, R., Eugenín-von Bernhardi, L., & Eugenín, J. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00124 · Cited by 556 · see citing works
“Several of those oxidative damage and changes result in a loss of function (Lovell et al., 2001; Halliwell, 2006).”
BackgroundMechanisms of Aβ Clearance and Degradation by Glial Cells
Ries, M., & Sastre, M. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00160 · Cited by 527 · see citing works
“NEP is mainly expressed in pre-synaptic terminals of neurons (Fukami et al., 2002) but can also be found in activated astrocytes (Fisk et al., 2007; Yamamoto et al., 2014) and microglia (Hickman et al., 2008).”
BackgroundAdvanced glycation endproducts and their receptor RAGE in Alzheimer's disease
Srikanth, V., Maczurek, A., Phan, T., Steele, M., Westcott, B., Juskiw, D., & Münch, G. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.04.016 · Cited by 524 · see citing works
Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation
Chen, Y., & Yu, Y. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02853-3 · Cited by 516 · see citing works
“However, sustained activation of microglia leads to the continuous release of inflammatory factors and reduces their ability to phagocytose and degrade neurotoxins, which in turn exacerbates Aβ accumulation, tau propagation, and neuronal death, ultimately promoting AD progression [5, 91, 92].”
BackgroundActivation of microglia and astrocytes: a roadway to neuroinflammation and Alzheimer’s disease
Kaur, D., Sharma, V., & Deshmukh, R. R. (2019) · Inflammopharmacology · doi:10.1007/s10787-019-00580-x · Cited by 493 · see citing works
Inflammation: the link between comorbidities, genetics, and Alzheimer’s disease
Newcombe, E. A., Camats-Perna, J., Silva, M. L., Valmas, N., Huat, T. J., & Medeiros, R. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1313-3 · Cited by 532 · see citing works
Krabbe, G., Halle, A., Matyash, V., Rinnenthal, J. L., Eom, G. D., Bernhardt, U., Miller, K. R., Prokop, S., Kettenmann, H., & Heppner, F. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060921 · Cited by 478 · see citing works
“Interestingly, expression of receptors and enzymes involved in microglial Ab-uptake and degradation is progressively downregulated in a transgenic mouse model of Alzheimer’s disease [20].”
BackgroundResultInfluentialRangaraju, S., Dammer, E. B., Raza, S. A., Rathakrishnan, P., Xiao, H., Gao, T., Duong, D. M., Pennington, M. W., Lah, J. J., Seyfried, N. T., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0254-8 · Cited by 430 · see citing works
“Despite effective uptake, Aβ clearance by microglia in AD may be ineffective despite phagocytic uptake [55].”
BackgroundKitazawa, M., Cheng, D., Tsukamoto, M. R., Koike, M. A., Wes, P. D., Vasilevko, V., Cribbs, D. H., & LaFerla, F. M. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100620 · Cited by 473 · see citing works
“For example, aging itself triggers differential activation in microglia isolated from the APP/PS1 transgenic mouse model (54, 67).”
BackgroundMetal Toxicity Links to Alzheimer's Disease and Neuroinflammation
Huat, T. J., Camats‐Perna, J., Newcombe, E. A., Valmas, N., Kitazawa, M., & Medeiros, R. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.01.018 · Cited by 483 · see citing works
The neuroinflammatory hypothesis of delirium
Cerejeira, J., Firmino, H., Vaz‐Serra, A., & Mukaetova‐Ladinska, E. B. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0674-1 · Cited by 482 · see citing works
“These changes are likely to impair Ab processing and removal by microglia, potentially contributing to accelerate the disease course [59].”
BackgroundCD22 blockade restores homeostatic microglial phagocytosis in ageing brains
Pluvinage, J. V., Haney, M. S., Smith, B. A. H., Sun, J., Iram, T., Bonanno, L., Li, L., Lee, D. P., Morgens, D. W., Yang, A. C., et al. (2019) · Nature · doi:10.1038/s41586-019-1088-4 · Cited by 459 · see citing works
The Role of Toll-Like Receptor 4 in Infectious and Noninfectious Inflammation
Molteni, M., Gemma, S., & Rossetti, C. (2016) · Mediators of Inflammation · doi:10.1155/2016/6978936 · Cited by 456 · see citing works
Amyloid toxicity in Alzheimer’s disease
Reiss, A. B., Arain, H. A., Stecker, M. M., Siegart, N. M., & Kasselman, L. J. (2018) · Reviews in the Neurosciences · doi:10.1515/revneuro-2017-0063 · Cited by 447 · see citing works
Inflammation, microglia, and alzheimer's disease
Cameron, B., & Landreth, G. E. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.10.006 · Cited by 440 · see citing works
“Hickman et al. (2008) have reported that the APPswe/PSEN1dE9 mouse has decreased expression of various Aβbinding receptors and degrading enzymes at 8 months of age that accompanies an increase in proinflammatory gene expression.”
BackgroundNeuroinflammatory processes in Alzheimer’s disease
Heneka, M. T., O’Banion, M. K., Terwel, D., & Kummer, M. P. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0438-z · Cited by 433 · see citing works
“…phagocytosis of Ab by microglia requires inflammatory signaling, but is obviously worn out during the course of the disease, in accordance with the finding that in 8-month-old APPswe/ PS1dE9 mice expression of Ab binding receptors and degrading enzymes in microglia is reduced (Hickman et al. 2008).”
ResultNorden, D. M., Muccigrosso, M. M., & Godbout, J. P. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.10.028 · Cited by 413 · see citing works
“For example, there was reduced phagocytosis of beta-amyloid by microglia from older AD transgenic mice (Hickman et al., 2008; Lee et al., 2010).”
BackgroundInhibition of IL-12/IL-23 signaling reduces Alzheimer's disease–like pathology and cognitive decline
vom Berg, J., Prokop, S., Miller, K. R., Obst, J., Kälin, R. E., Lopategui-Cabezas, I., Wegner, A., Mair, F., Schipke, C. G., Peters, O., et al. (2012) · Nature Medicine · doi:10.1038/nm.2965 · Cited by 416 · see citing works
Stansley, B., Post, J., & Hensley, K. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-115 · Cited by 419 · see citing works
Marsh, S. E., Abud, E. M., Lakatos, A., Karimzadeh, A., Yeung, S. T., Davtyan, H., Fote, G. M., Lau, L., Weinger, J. G., Lane, T. E., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525466113 · Cited by 411 · see citing works
“However, chronic activation of these cells shift microglia to a more proinflammatory and less phagocytic state (9, 10).”
BackgroundTREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer's Disease
Griciuc, A., Patel, S., Federico, A. N., Choi, S. H., Innes, B. J., Oram, M. K., Cereghetti, G., McGinty, D., Anselmo, A., Sadreyev, R. I., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.06.010 · Cited by 378 · see citing works
“While microglia can clear amyloid beta (Aβ), they can also release pro-inflammatory cytokines leading to neuroinflammation (Hansen et al., 2018; Hickman et al., 2008).”
BackgroundSelf-citationPreparing Synthetic Aβ in Different Aggregation States
Stine, W. B., Jungbauer, L., Yu, C., & LaDu, M. J. (2010) · Methods in Molecular Biology · doi:10.1007/978-1-60761-744-0_2 · Cited by 403 · see citing works
Neuroprotective strategies involving ROS in Alzheimer disease
Dumont, M., & Beal, M. F. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.11.026 · Cited by 402 · see citing works
“In the same animals, microglial levels of proinflammatory cytokines interleukin-1β and tumor necrosis factor alpha were markedly increased [122].”
BackgroundMicroglia Priming with Aging and Stress
Niraula, A., Sheridan, J. F., & Godbout, J. P. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.185 · Cited by 398 · see citing works
Isolation of glia from Alzheimer’s mice reveals inflammation and dysfunction
Orre, M., Kamphuis, W., Osborn, L. M., Jansen, A. H. P., Kooijman, L., Bossers, K., & Hol, E. M. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.06.004 · Cited by 394 · see citing works
“Chronic microglia activation has also previously been linked to a reduced phagocytic capacity of Ab, and reduced expression of Ab binding receptors (Hickman et al., 2008), which is in line with the reduction of genes involved in endocytosis.”
Ghosh, S., Wu, M. D., Shaftel, S. S., Kyrkanides, S., LaFerla, F. M., Olschowka, J. A., & O'Banion, M. K. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.4361-12.2013 · Cited by 390 · see citing works
“It has been proposed that accumulation of A plaques results from decreased clearance by dysfunctional microglia (Hickman et al., 2008) and that microglial-mediated A clearance depends on their activation phenotype (Colton, 2009).”
BackgroundGarwood, C. J., Pooler, A. M., Atherton, J., Hanger, D. P., & Noble, W. (2011) · Cell Death & Disease · doi:10.1038/cddis.2011.50 · Cited by 379 · see citing works
“Phagocytosis of Ab by microglia is believed to be a protective mechanism,9 at least in younger animals;10 however, neuronal loss also results from increased pro-inflammatory cytokine production by microglia in models of AD.10 In addition to the influence of microglia, an important role of astrocytes in regulating Ab-i…”
BackgroundInfluentialMicroglia and Inflammation in Alzheimers Disease
Mandrekar-Colucci, S., & Landreth, G. E. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710791012071 · Cited by 421 · see citing works
“The fall in receptor levels was postulated to be due to the increase in levels of pro-inflammatory cytokines, as incubation of N9 microglial cells with TNFα decreased the expression of scavenger receptor A and CD36 and reduced Aβ uptake by cultured microglial cells [92].”
BackgroundCSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease
Janelidze, S., Mattsson, N., Stomrud, E., Lindberg, O., Palmqvist, S., Zetterberg, H., Blennow, K., & Hansson, O. (2018) · Neurology · doi:10.1212/wnl.0000000000006082 · Cited by 359 · see citing works
Ferreira, S. T., Lourenco, M. V., Oliveira, M. M., & De Felice, F. G. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00191 · Cited by 373 · see citing works
“AβOs also target microglia to promote TNF-α and IL-1β release (Ledo et al., 2013).”
BackgroundInfluentialIL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline
Fu, A. K. Y., Hung, K.-W., Yuen, M. Y. F., Zhou, X., Mak, D. S. Y., Chan, I. C. W., Cheung, T. H., Zhang, B., Fu, W.-Y., Liew, F. Y., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1604032113 · Cited by 369 · see citing works
“Interestingly, the Aβ-clearing capacity of microglia in APP/PS1 mice is impaired with aging, as revealed by reduced expression of Aβ-binding receptors and Aβdegrading enzymes (37).”
BackgroundTargeting p38 MAPK pathway for the treatment of Alzheimer's disease
Munoz, L., & Ammit, A. J. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.11.010 · Cited by 370 · see citing works
“Furthermore, inhibition of p38 MAPK activation effectively blocked Ab-induced synaptic depression (Hsieh et al., 2006).”
BackgroundMontgomery, S. L., & Bowers, W. J. (2011) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-011-9287-2 · Cited by 365 · see citing works
“For example, CD14 expression positively correlates with TNFα levels, whereas CD36 negatively correlates with TNF-α (Liu et al. 2005a; Hickman et al. 2008).”
BackgroundSalminen, A., Kaarniranta, K., Kauppinen, A., Ojala, J. O., Haapasalo, A., Soininen, H. S., & Hiltunen, M. O. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.06.002 · Cited by 366 · see citing works
A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease
Hampel, H., Caraci, F., Cuello, A. C., Caruso, G., Nisticò, R., Corbo, M., Baldacci, F., Toschi, N., Garaci, F., Chiesa, P. A., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00456 · Cited by 360 · see citing works
Advanced bioactive nanomaterials for biomedical applications
Zhao, Y., Zhang, Z., Pan, Z., & Liu, Y. (2021) · Exploration · doi:10.1002/exp.20210089 · Cited by 359 · see citing works
Cai, Y., Liu, J., Wang, B., Sun, M., & Yang, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.856376 · Cited by 351 · see citing works
“Subsequently, evidence for an important role of RAGE from a study demonstrated that, a flavoring agent vanillic acid (VA), could antagonize RAGE-mediated c-Jun N-terminal kinase (JNK).”
BackgroundInfluentialMicroglia Function in Alzheimer’s Disease
Solito, E., & Sastre, M. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00014 · Cited by 347 · see citing works
“In addition, microglia from old transgenic mice have a decrease in the expression of the Aβ-binding SR-A, CD36 and RAGE, and the Aβ degrading enzymes IDE, neprilysin, and matrix metalloprotease 9 (MMP9), compared with wild-type controls (Hickman et al., 2008).”
BackgroundDoens, D., & Fernández, P. L. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-48 · Cited by 348 · see citing works
“SR-A Microglia, astrocytes Aβ internalization and clearance [85,88]”
BackgroundMethodInfluentialSalminen, A., Ojala, J. O., Kauppinen, A., Kaarniranta, K., & Suuronen, T. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.01.001 · Cited by 350 · see citing works
Chakrabarty, P., Jansen‐West, K., Beccard, A., Ceballos‐Diaz, C., Levites, Y., Verbeeck, C., Zubair, A. C., Dickson, D., Golde, T. E., & Das, P. (2010) · The FASEB Journal · doi:10.1096/fj.09-141754 · Cited by 328 · see citing works
Luo, R., Su, L.-Y., Li, G., Yang, J., Liu, Q., Yang, L.-X., Zhang, D.-F., Zhou, H., Xu, M., Fan, Y., et al. (2020) · Autophagy · doi:10.1080/15548627.2019.1596488 · Cited by 364 · see citing works
“Activation of microglia by intracranial delivery of lipopolysaccharide or pro-inflammatory cytokines mitigated Aβ deposition [86–88], and microglial dysfunction led to a defective Aβ clearance in AD mice [91] and accelerated progression of AD-like disease in mice [92].”
BackgroundMicroglia Phenotypes in Aging and Neurodegenerative Diseases
Wendimu, M. Y., & Hooks, S. B. (2022) · Cells · doi:10.3390/cells11132091 · Cited by 336 · see citing works
Njie, E. G., Boelen, E., Stassen, F. R., Steinbusch, H. W. M., Borchelt, D. R., & Streit, W. J. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.05.008 · Cited by 335 · see citing works
“These protocols either trap microglia using antibodies to cell-specific antigens (Hickman et al., 2008; Tham et al., 2003) or separate microglia using density centrifugation (de Haas et al., 2007; Frank et al., 2006).”
InfluentialInnate Immunity and Neurodegeneration
Labzin, L. I., Heneka, M. T., & Latz, E. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-050715-104343 · Cited by 319 · see citing works
Myeloid Cells in the Central Nervous System
Herz, J., Filiano, A. J., Wiltbank, A. T., Yogev, N., & Kipnis, J. (2017) · Immunity · doi:10.1016/j.immuni.2017.06.007 · Cited by 332 · see citing works
“This view was initially challenged by research in the peripheral nervous system, where macrophages play important roles in clearing myelin debris and supporting neural regeneration after injury (Hirata et al., 1999; Keilhoff et al., 2007; Venezie et al., 1995).”
BackgroundThe Microbiota–Gut–Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame?
Megur, A., Baltriukienė, D., Bukelskienė, V., & Burokas, A. (2020) · Nutrients · doi:10.3390/nu13010037 · Cited by 323 · see citing works
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“Multiple lines of evidence have suggested that amyloid plaques accumulate and persist because dysfunctional microglia are unable to remove them [3,56,161-163].”
BackgroundInflammation and Alzheimer’s disease
Lee, Y.-J., Han, S. B., Nam, S.-Y., Oh, K.-W., & Hong, J. T. (2010) · Archives of Pharmacal Research · doi:10.1007/s12272-010-1006-7 · Cited by 396 · see citing works
“…addition, microglia from old transgenic mice show decreased expression of Aβ-binding scavenger receptors A (SRA), CD36 and RAGE, and the Aβ-degrading enzyme (insulin degrading enzyme [IDE]), neprilysin and Matrix metalloproteinases 9 (MMP9), compared with wild-type controls (Hickman et al., 2008).”
BackgroundResultInfluentialMicroglia–blood vessel interactions: a double-edged sword in brain pathologies
Dudvarski Stankovic, N., Teodorczyk, M., Ploen, R., Zipp, F., & Schmidt, M. H. H. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1524-y · Cited by 301 · see citing works
Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging
Plaza-Zabala, A., Sierra-Torre, V., & Sierra, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18030598 · Cited by 323 · see citing works
Adolfsson, O., Pihlgren, M., Toni, N., Varisco, Y., Buccarello, A. L., Antoniello, K., Lohmann, S., Piorkowska, K., Gafner, V., Atwal, J. K., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.4742-11.2012 · Cited by 317 · see citing works
“Microglia play a crucial role in uptake and degradation of A , a function that is postulated to be compromised in APP transgenic mice (Hickman et al., 2008).”
BackgroundChronic stress and glucocorticoids: From neuronal plasticity to neurodegeneration
Vyas, S., Rodrigues, A. J., Silva, J. M., Tronche, F., Almeida, O. F. X., Sousa, N., & Sotiropoulos, I. (2016) · Neural Plasticity · doi:10.1155/2016/6391686 · Cited by 297 · see citing works
Microglia in Health and Disease
Ransohoff, R. M., & Khoury, J. E. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020560 · Cited by 303 · see citing works
RETRACTED: Neuroinflammatory Markers: Key Indicators in the Pathology of Neurodegenerative Diseases
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“However, Aβ accumulation and sustained pro-inflammatory cytokine initiation induce nerve cell damage [66,67].”
BackgroundRetractedNeuroinflammation in Alzheimer’s Disease
Onyango, I. G., Jauregui, G. V., Čarná, M., Bennett, J. P., & Stokin, G. B. (2021) · Biomedicines · doi:10.3390/biomedicines9050524 · Cited by 330 · see citing works
Microglial phenotypes in Parkinson’s disease and animal models of the disease
Joers, V., Tansey, M. G., Mulas, G., & Carta, A. R. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.04.006 · Cited by 285 · see citing works
“Microglia Aβ-binding scavenger receptors that are largely involved in Aβ plaque clearance were downregulated in aged Alzheimer’s disease mice (Hickman et al., 2008), suggesting alterations in microglial receptors may be a process that coincides with a shift in morphology.”
BackgroundLee, J. K., Jin, H. K., Endo, S., Schuchman, E. H., Carter, J., & Bae, J.-S. (2009) · Stem Cells · doi:10.1002/stem.277 · Cited by 303 · see citing works
Salminen, A., Ojala, J. O., Kaarniranta, K., & Kauppinen, A. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-0962-0 · Cited by 304 · see citing works
Microglia actions in Alzheimer's disease
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“caused by chronic (inflammatory) stimulation [63] and/or the presence of Ab [77], culminating in a state of cellular senescence [139].”
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“These cytokines may in turn act in an autocrine manner and promote Ab production by stimulating b- and g-secretases and/or reduce Ab clearance by reducing expression of Ab-binding receptors and Ab-degrading enzymes [38,39].”
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“The local environment, and possibly intrinsic changes to the microglia determine how the cells will respond to the activating signals [7,8].”
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Amyloid β-Induced Death in Neurons Involves Glial and Neuronal Hemichannels
Orellana, J. A., Shoji, K. F., Abudara, V., Ezan, P., Amigou, E., Sáez, P. J., Jiang, J. X., Naus, C. C. G., Sáez, J. C., & Giaume, C. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6417-10.2011 · Cited by 286 · see citing works
“In addition, these cytokines are produced by A -treated microglia (Meda et al., 1999) and their mRNA expression is increased in these cells at amyloid plaques (Hickman et al., 2008).”
BackgroundPan, R., Ma, J., Kong, X.-X., Wang, X., Li, S., Qi, X., Yan, Y., Cheng, J., Liu, Q., Jin, W., et al. (2019) · Science Advances · doi:10.1126/sciadv.aau6328 · Cited by 290 · see citing works
- 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
- Health Sciences › Medicine › Physiology › 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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