Ex vivo cultures of microglia from young and aged rodent brain reveal age-related changes in microglial function
Open accessAbstract
To understand how microglial cell function may change with aging, various protocols have been developed to isolate microglia from the young and aged central nervous system (CNS). Here we report modification of an existing protocol that is marked by less debris contamination and improved yields and demonstrate that microglial functions are varied and dependent on age. Specifically, we found that microglia from aged mice constitutively secrete greater amounts of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) relative to microglia from younger mice and are less responsive to stimulation. Also, microglia from aged mice have reduced glutathione levels and internalize less amyloid beta peptide (Aβ) while microglia from mice of all ages do not retain the amyloid beta peptide for a significant length of time. These studies offer further support for the idea that microglial cell function changes with aging. They suggest that microglial Aβ phagocytosis results in Aβ redistribution rather than biophysical degradation in vivo and thereby provide mechanistic insight to the lack of amyloid burden elimination by parenchymal microglia in aged adults and those suffering from Alzheimer's disease.
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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 [76]
The Discussion (page unavailable) reports a 2- to 4-fold age-related decrease in Aβ internalization by microglia from aged mice, supporting the aging portion of the claim. The paper does not show that chronic Aβ exposure or sustained inflammation in the AD brain causes a decline in phagocytic capacity; it discusses AD as a possible implication of its age-related findings. (LLM, conf=0.90)
Experimental — accuracy not yet measuredPerturbations in microglial activity, often associated with aging, can affect the effective clearance of neuron-derived Aβ fibrils, leading to increased plaque formation and progression of cognitive and behavioral impairments.
“However, perturbations in microglial activity, often associated with aging, can affect the effective clearance of these neuron-derived Aβ fibrils, leading to increased plaque formation and the progression of cognitive and behavioral impairments (17–20).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [20]
The Results and Discussion (pages not specified in our copy) report that aged microglia internalize less Aβ42 and propose that this could leave more Aβ available for plaque formation. The tested Aβ42 preparation contained several forms, including likely fibrils; the paper does not establish reduced clearance of fibrils specifically or link the proposed plaque increase to progression of cognitive and behavioral impairments. (LLM, conf=0.87)
Experimental — accuracy not yet measuredMicroglia from the aged brain internalized 53% fewer amyloid beta plaques compared with the young brain, suggesting inefficient phagocytosis in aged microglia.
“Furthermore, compared with the young brain, microglia from the aged brain were found to internalize 53% fewer amyloid beta plaques, suggesting inefficient phagocytosis in aged microglia (Njie et al, 2012).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Njie et al, 2012
Aged microglia also expressed significantly higher levels of TNFα and IL6 in response to ex vivo LPS.
“aged microglia also expressed significantly higher levels of TNFα and IL6 in response to ex vivo LPS (Njie et al, 2012).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Njie et al, 2012
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Cites
Tietze, F. (1969) · Analytical Biochemistry · doi:10.1016/0003-2697(69)90064-5 · Cited by 6,077 · see citing works
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632 · see citing works
Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective
Tanzi, R. E., & Bertram, L. (2005) · Cell · doi:10.1016/j.cell.2005.02.008 · Cited by 1,849 · see citing works
Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
Boillée, S., Yamanaka, K., Lobsiger, C. S., Copeland, N. G., Jenkins, N. A., Kassiotis, G., Kollias, G., & Cleveland, D. W. (2006) · Science · doi:10.1126/science.1123511 · Cited by 1,623 · see citing works
Microglial Dysfunction and Defective β-Amyloid Clearance Pathways in Aging Alzheimer's Disease Mice
Hickman, S. E., Allison, E. K., & El Khoury, J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0616-08.2008 · Cited by 1,329 · cited 4× · 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).”
InfluentialmRNA stability in mammalian cells
Ross, J. (1995) · Microbiological Reviews · doi:10.1128/mr.59.3.423-450.1995 · Cited by 1,324 · see citing works
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 · see citing works
Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions
Mildner, A., Schmidt, H., Nitsche, M., Merkler, D., Hanisch, U.-K., Mack, M., Heikenwalder, M., Brück, W., Priller, J., & Prinz, M. (2007) · Nature Neuroscience · doi:10.1038/nn2015 · Cited by 1,089 · see citing works
Microglia and neuroinflammation: a pathological perspective
Streit (2004) · Journal of Neuroinflammation · doi:10.1186/1742-2094-1-14 · Cited by 1,039 · see citing works
Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer’s disease
Meyer-Luehmann, M., Spires-Jones, T. L., Prada, C., Garcia-Alloza, M., de Calignon, A., Rozkalne, A., Koenigsknecht-Talboo, J., Holtzman, D. M., Bacskai, B. J., & Hyman, B. T. (2008) · Nature · doi:10.1038/nature06616 · Cited by 987 · see citing works
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 · see citing works
Streit, W. J., Braak, H., Xue, Q.-S., & Bechmann, I. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0556-6 · Cited by 727 · see citing works
Self-citationMicroglia derived from aging mice exhibit an altered inflammatory profile
Sierra, A., Gottfried‐Blackmore, A. C., McEwen, B. S., & Bulloch, K. (2007) · Glia · doi:10.1002/glia.20468 · Cited by 688 · see citing works
Neuropathology of nondemented aging: presumptive evidence for preclinical Alzheimer disease
Price, J. L., McKeel, D. W., Buckles, V. D., Roe, C. M., Xiong, C., Grundman, M., Hansen, L. A., Petersen, R. C., Parisi, J. E., Dickson, D. W., et al. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.04.002 · Cited by 661 · see citing works
Microglial response to amyloid plaques in APPsw transgenic mice.
Frautschy, S. A., Yang, F., Irrizarry, M., Hyman, B. T., Saido, T. C., Hsiao, K., & Cole, G. M. (1998) · Europe PMC (PubMed Central) · Cited by 592 · see citing works
Qin, L., Liu, Y., Wang, T., Wei, S.-J., Block, M. L., Wilson, B., Liu, B., & Hong, J.-S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307657200 · Cited by 574 · see citing works
Dynamics of the Microglial/Amyloid Interaction Indicate a Role in Plaque Maintenance
Bolmont, T., Haiss, F., Eicke, D., Radde, R., Mathis, C. A., Klunk, W. E., Kohsaka, S., Jucker, M., & Calhoun, M. E. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4814-07.2008 · Cited by 526 · see citing works
Evidence for synthesis of scrapie prion proteins in the endocytic pathway.
Borchelt, D., Taraboulos, A., & Prusiner, S. B. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41985-0 · Cited by 500 · see citing works
Self-citationA High Plasma Concentration of TNF- Is Associated With Dementia in Centenarians
Brüünsgaard, H., Andersen‐Ranberg, K., Jeune, B., Pedersen, B. K., Skinhøj, P., & Pedersen, B. K. (1999) · The Journals of Gerontology Series A · doi:10.1093/gerona/54.7.m357 · Cited by 458 · see citing works
Cerebral Interleukin-6 is Neuroprotective during Permanent Focal Cerebral Ischemia in the Rat
Loddick, S. A., Turnbull, A. V., & Rothwell, N. J. (1998) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199802000-00008 · Cited by 418 · see citing works
Increase of plasma IL-6 concentration with age in healthy subjects
Wei, J., Xu, H., Davies, J. L., & Hemmings, G. P. (1992) · Life Sciences · doi:10.1016/0024-3205(92)90112-3 · Cited by 402 · see citing works
Formation and maintenance of Alzheimer's disease β-amyloid plaques in the absence of microglia
Grathwohl, S. A., Kälin, R. E., Bolmont, T., Prokop, S., Winkelmann, G., Kaeser, S. A., Odenthal, J., Radde, R., Eldh, T., Gandy, S., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2432 · Cited by 401 · see citing works
Licastro, F., Pedrini, S., Caputo, L., Annoni, G., Davis, L. J., Ferri, C., Casadei, V. M., & Grimaldi, L. M. E. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00226-x · Cited by 400 · see citing works
Microglia and inflammatory mechanisms in the clearance of amyloid β peptide
Rogers, J., Strohmeyer, R., Kovelowski, C. J., & Li, R. (2002) · Glia · doi:10.1002/glia.10153 · Cited by 381 · see citing works
Simard, A. R., & Rivest, S. (2004) · The FASEB Journal · doi:10.1096/fj.04-1517fje · Cited by 354 · see citing works
Tarkowski, E., Blennow, K., Wallin, A., & Tarkowski, A. (1999) · Journal of Clinical Immunology · doi:10.1023/a:1020568013953 · Cited by 349 · see citing works
Sympathetic neurons can produce and respond to interleukin 6.
März, P., Cheng, J. G., Gadient, R., Patterson, P. H., Stoyan, T., Otten, U., & Rose-John, S. (1998) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.95.6.3251 · Cited by 346 · see citing works
Mast cells disrupt epithelial barrier function during enteric nematode infection
McDermott, J. R., Bartram, R. E., Knight, P. A., Miller, H. R. P., Garrod, D. R., & Grencis, R. K. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1231488100 · Cited by 346 · see citing works
Increased interleukin-6 expression by microglia from brain of aged mice
Ye, S.-M., & Johnson, R. W. (1999) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00217-3 · Cited by 326 · see citing works
Bouras, C., Hof, P. R., Giannakopoulos, P., Michel, J.-P., & Morrison, J. H. (1994) · Cerebral Cortex · doi:10.1093/cercor/4.2.138 · Cited by 280 · see citing works
Simmons, D. A., Casale, M., Alcon, B., Pham, N., Narayan, N., & LYNCH, G. S. (2007) · Glia · doi:10.1002/glia.20526 · Cited by 277 · see citing works
Evidence That Aging And Amyloid Promote Microglial Cell Senescence
Flanary, B. E., Sammons, N. W., Nguyen, C., Walker, D., & Streit, W. J. (2007) · Rejuvenation Research · doi:10.1089/rej.2006.9096 · Cited by 272 · see citing works
Self-citationOxidative and Antioxidative Potential of Brain Microglial Cells
Dringen, R. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.1223 · Cited by 271 · see citing works
Activation of Microglia Acidifies Lysosomes and Leads to Degradation of Alzheimer Amyloid Fibrils
Majumdar, A., Cruz, D., Asamoah, N., Buxbaum, A., Sohar, I., Lobel, P., & Maxfield, F. R. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-10-0975 · Cited by 271 · see citing works
Jankowsky, J. L., Slunt, H. H., Gonzales, V., Savonenko, A. V., Wen, J. C., Jenkins, N. A., Copeland, N. G., Younkin, L. H., Lester, H. A., Younkin, S. G., et al. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020355 · Cited by 237 · see citing works
Self-citationChung, H., Brazil, M. I., Soe, T. T., & Maxfield, F. R. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.45.32301 · Cited by 212 · see citing works
Polymorphisms in Inflammatory Genes and the Risk of Alzheimer Disease
McGeer, P. L. (2001) · Archives of Neurology · doi:10.1001/archneur.58.11.1790 · Cited by 192 · see citing works
Li, J., Galvis, M. L. E., Gong, F., Zhang, X., Zcharia, E., Metzger, S., Vlodavsky, I., Kisilevsky, R., & Lindahl, U. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502287102 · Cited by 180 · see citing works
Wei, L., Kuo, M., Chen, C., et al. (2001) · Oncogene · doi:10.1038/sj.onc.1204733 · Cited by 175 · see citing works
Frank, M. G., Wieseler‐Frank, J., Watkins, L. R., & Maier, S. F. (2005) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2005.06.026 · Cited by 164 · see citing works
Microglial degeneration in the aging brain - bad news for neurons?
Streit, W. (2008) · Frontiers in Bioscience · doi:10.2741/2937 · Cited by 150 · see citing works
Self-citationCLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia
Milton, R. H., Abeti, R., Averaimo, S., Debiasi, S., Vitellaro‐Zuccarello, L., Jiang, L., Curmi, P. M. G., Breit, S. N., Duchen, M. R., & Mazzanti, M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2431-08.2008 · Cited by 148 · see citing works
Uhm, J. H., Dooley, N. P., Oh, L. Y. S., & Yong, V. W. (1998) · Glia · doi:10.1002/(sici)1098-1136(199801)22:1 · Cited by 144 · see citing works
Vincent, V. A. M., Tilders, F. J. H., & van Dam, A.-M. (1997) · Glia · doi:10.1002/(sici)1098-1136(199703)19:3 · Cited by 123 · see citing works
Microglial activation state and lysophospholipid acid receptor expression
Tham, C., Lin, F., Rao, T. S., Yu, N., & Webb, M. (2003) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2003.09.003 · Cited by 119 · see citing works
Zaghi, J., Goldenson, B., Inayathullah, M., Lossinsky, A. S., Masoumi, A., Avagyan, H., Mahanian, M., Bernas, M. J., Weinand, M. E., Rosenthal, M. J., et al. (2009) · Acta Neuropathologica · doi:10.1007/s00401-008-0481-0 · Cited by 115 · see citing works
Li, L., Lu, J., Tay, S. S. W., Moochhala, S., & He, B. P. (2007) · Brain Research · doi:10.1016/j.brainres.2007.04.066 · Cited by 110 · see citing works
Wnt-1 dependent activation of the survival factor NF-?B in PC12 cells
Bournat, J. C., Brown, A. M. C., & Soler, A. P. (2000) · Journal of Neuroscience Research · doi:10.1002/1097-4547(20000701)61:1 · Cited by 100 · see citing works
Activated microglia (BV-2) facilitation of TNF-α-mediated motor neuron death in vitro
He, B. P., Wen, W., & Strong, M. J. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00141-8 · Cited by 98 · see citing works
Hirrlinger, J., Gutterer, J. M., Kußmaul, L., Hamprecht, B., & Dringen, R. (2000) · Developmental Neuroscience · doi:10.1159/000017464 · Cited by 92 · see citing works
IFN Regulatory Factor-1 Regulates IFN-γ-Dependent Cathepsin S Expression
Gravesande, K. S. V., Layne, M. D., Ye, Q., Le, L., Baron, R. M., Perrella, M. A., Santambrogio, L., Silverman, E. S., & Riese, R. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.9.4488 · Cited by 90 · see citing works
Lysosomal processing of amyloid precursor protein to Aβ peptides: a distinct role for cathepsin S
Munger, J. S., Haass, C., Lemere, C. A., Shi, G., Wong, W., Teplow, D. B., Selkoe, D. J., & Chapman, H. A. (1995) · Biochemical Journal · doi:10.1042/bj3110299 · Cited by 85 · see citing works
Ponomarev, E. D., Novikova, M., Maresz, K., Shriver, L. P., & Dittel, B. N. (2005) · Journal of Immunological Methods · doi:10.1016/j.jim.2005.02.011 · Cited by 82 · see citing works
De Haas, A. H., Boddeke, H. W. G. M., Brouwer, N., & Biber, K. (2007) · Glia · doi:10.1002/glia.20554 · Cited by 81 · see citing works
ELISA Method for Measurement of Amyloid-β Levels
Schmidt, S. D., Nixon, R. A., & Mathews, P. M. (2005) · Humana Press eBooks · doi:10.1385/1-59259-874-9:279 · Cited by 75 · see citing works
Chen, H., McCarty, D. M., Bruce, A. T., Suzuki, K., & Suzuki, K. (1999) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19990215)55:4 · Cited by 71 · see citing works
Tumour necrosis factor-α gene polymorphisms and Alzheimer's disease
Culpan, D., MacGowan, S. H., Ford, J. M., Nicoll, J. A. R., Griffin, W. S. T., Dewar, D., Cairns, N. J., Hughes, A., Kehoe, P. G., & Wilcock, G. K. (2003) · Neuroscience Letters · doi:10.1016/s0304-3940(03)00854-1 · Cited by 67 · see citing works
Astrocytic Alterations in Interleukin-6/Soluble Interleukin-6 Receptor α Double-Transgenic Mice
Brunello, A., Weissenberger, J., Каппелер, А., et al. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64787-6 · Cited by 63 · see citing works
Esen, N., & Kielian, T. (2007) · Journal of Neuroinflammation · doi:10.1186/1742-2094-4-10 · Cited by 59 · see citing works
Hu, B., Yip, H. K.-F., & So, K. (1998) · Glia · doi:10.1002/(sici)1098-1136(199810)24:2 · Cited by 58 · see citing works
Tchaikovskaya, T. L., Fraifeld, V. E., Urphanishvili, T., Andorfer, J. H., Davies, P., & Listowsky, I. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.08.029 · Cited by 48 · see citing works
Uptake of fibrillar β-amyloid by microglia isolated from MSR-A (type I and type II) knockout mice
Chung, H., Brazil, M. I., Irizarry, M. C., Hyman, B. T., & Maxfield, F. R. (2001) · Neuroreport · doi:10.1097/00001756-200105080-00020 · Cited by 46 · see citing works
Cdk5 regulates activation and localization of Src during corneal epithelial wound closure
Gao, C., Stepp, M. A., Fariss, R. N., et al. (2004) · Journal of Cell Science · doi:10.1242/jcs.01271 · Cited by 45 · see citing works
Stolzing, A., Widmer, R., Jung, T., Voß, P., & Grune, T. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.02.011 · Cited by 32 · see citing works
Jonnal (2000) · doi:10.1002/1096-8628(20001204)96:6
Flagged first, then by citations
Cited by
Sorted by citations
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
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
Regulation and function of adult neurogenesis: from genes to cognition.
Aimone, J. B., Li, Y., Lee, S. W., Clemenson, G. D., Deng, W., & Gage, F. H. (2014) · Physiological Reviews · doi:10.1152/physrev.00004.2014 · Cited by 635 · 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
Age-related alterations in the dynamic behavior of microglia
Damani, M. R., Zhao, L., Fontainhas, A. M., Amaral, J., Fariss, R. N., & Wong, W. T. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2010.00660.x · Cited by 504 · see citing works
Deciphering the mechanism underlying late-onset Alzheimer disease
Krstic, D., & Knuesel, I. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.236 · Cited by 457 · 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
Norden, D. M., Muccigrosso, M. M., & Godbout, J. P. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.10.028 · Cited by 413 · see citing works
Microglia 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
Homeostatic and injury‐induced microglia behavior in the aging brain
Hefendehl, J. K., Neher, J. J., Sühs, R. B., Kohsaka, S., Skodras, A., & Jucker, M. (2014) · Aging Cell · doi:10.1111/acel.12149 · Cited by 319 · see citing works
Streit, W. J., Xue, Q.-S., Tischer, J., & Bechmann, I. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0142-6 · Cited by 317 · see citing works
Self-citationMicroglia actions in Alzheimer's disease
Prokop, S., Miller, K. R., & Heppner, F. L. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1182-x · Cited by 291 · see citing works
Immunosenescence of microglia and macrophages: impact on the ageing central nervous system
Rawji, K. S., Mishra, M. K., Michaels, N. J., Rivest, S., Stys, P. K., & Yong, V. W. (2016) · Brain · doi:10.1093/brain/awv395 · Cited by 252 · see citing works
Microglia Modulate Hippocampal Neural Precursor Activity in Response to Exercise and Aging
Vukovic, J., Colditz, M. J., Blackmore, D. G., Ruitenberg, M. J., & Bartlett, P. F. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5925-11.2012 · Cited by 241 · see citing works
Parkinson’s disease as a result of aging
Rodriguez, M., Rodriguez‐Sabate, C., Morales, I., Sanchez, A., & Sabate, M. (2015) · Aging Cell · doi:10.1111/acel.12312 · Cited by 214 · see citing works
Increased White Matter Inflammation in Aging- and Alzheimer’s Disease Brain
Raj, D., Yin, Z., Breur, M., Doorduin, J., Holtman, I. R., Olah, M., Mantingh-Otter, I. J., Van Dam, D., De Deyn, P. P., den Dunnen, W., et al. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00206 · Cited by 180 · see citing works
Dysregulated neuronal–microglial cross-talk during aging, stress and inflammation
Jurgens, H. A., & Johnson, R. W. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2010.11.014 · Cited by 179 · see citing works
Ritzel, R. M., Doran, S. J., Glaser, E. P., Meadows, V. E., Faden, A. I., Stoica, B. A., & Loane, D. J. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.02.010 · Cited by 156 · see citing works
Microglia change from a reactive to an age-like phenotype with the time in culture
Caldeira, C., Oliveira, A. F., Cunha, C., Vaz, A. R., Falcão, A. S., Fernandes, A., & Brites, D. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00152 · Cited by 156 · see citing works
Dysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic neuroinflammation
Chu, E., Mychasiuk, R., Hibbs, M. L., & Semple, B. D. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02325-6 · Cited by 152 · see citing works
Microglial priming of antigen presentation and adaptive stimulation in Alzheimer’s disease
Das, R., & Chinnathambi, S. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03132-2 · Cited by 147 · see citing works
Brelstaff, J. H., Mason, M., Katsinelos, T., McEwan, W. A., Ghetti, B., Tolkovsky, A. M., & Spillantini, M. G. (2021) · Science Advances · doi:10.1126/sciadv.abg4980 · Cited by 135 · see citing works
Abutbul, S., Shapiro, J., Szaingurten‐Solodkin, I., Levy, N., Carmy, Y., Baron, R., Jung, S., & Monsonego, A. (2012) · Glia · doi:10.1002/glia.22343 · Cited by 122 · see citing works
Microglia in Aging and Alzheimer’s Disease: A Comparative Species Review
Edler, M. K., Mhatre-Winters, I., & Richardson, J. R. (2021) · Cells · doi:10.3390/cells10051138 · Cited by 126 · see citing works
Opposing Effects of Membrane-Anchored CX3CL1 on Amyloid and Tau Pathologies via the p38 MAPK Pathway
Lee, S., Xu, G., Jay, T. R., Bhatta, S., Kim, K.-W., Jung, S., Landreth, G. E., Ransohoff, R. M., & Lamb, B. T. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0853-14.2014 · Cited by 123 · see citing works
Hippocampal expression of murine TNFα results in attenuation of amyloid deposition in vivo
Chakrabarty, P., Herring, A., Ceballos-Diaz, C., Das, P., & Golde, T. E. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-16 · Cited by 117 · see citing works
Carrillo-de Sauvage, M. Á., Maatouk, L., Arnoux, I., Pasco, M., Sanz Diez, A., Delahaye, M., Herrero, M. T., Newman, T. A., Calvo, C. F., Audinat, E., et al. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2013.108 · Cited by 114 · see citing works
Prakash, P., Manchanda, P., Paouri, E., Bisht, K., Sharma, K., Rajpoot, J., Wendt, V., Hossain, A., Wijewardhane, P. R., Randolph, C. E., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.04.029 · Cited by 104 · see citing works
Aging and sex: Impact on microglia phagocytosis
Yanguas‐Casás, N., Crespo‐Castrillo, A., Arevalo, M., & Garcia‐Segura, L. M. (2020) · Aging Cell · doi:10.1111/acel.13182 · Cited by 93 · see citing works
Human CNS immune senescence and neurodegeneration
Streit, W. J., & Xue, Q.-S. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.05.005 · Cited by 86 · see citing works
Self-citationSenescent Microglia: The Key to the Ageing Brain?
Greenwood, E. K., & Brown, D. R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094402 · Cited by 84 · see citing works
Marlatt, M. W., Bauer, J., Aronica, E., van Haastert, E. S., Hoozemans, J. J. M., Joels, M., & Lucassen, P. J. (2014) · Neural Plasticity · doi:10.1155/2014/693851 · Cited by 83 · see citing works
“Ex vivo microglia cultures isolated from aged mice, for example, show elevated production of the proinflammatory molecules Il-6 and TNF-α, while microglia from old animals have a decreased ability to internalize Aβ compared to cells isolated from young animals [70].”
BackgroundNorden, D. M., Trojanowski, P. J., Walker, F. R., & Godbout, J. P. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.04.014 · Cited by 73 · see citing works
Suridjan, I., Rusjan, P. M., Voineskos, A. N., Selvanathan, T., Setiawan, E., Strafella, A. P., Wilson, A. A., Meyer, J. H., Houle, S., & Mizrahi, R. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2013.09.021 · Cited by 71 · see citing works
Phenotypic and functional differences between senescent and aged murine microglia
Stojiljkovic, M. R., Ain, Q., Bondeva, T., Heller, R., Schmeer, C., & Witte, O. W. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.10.007 · Cited by 71 · see citing works
Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model
Wu, X., Miller, J. A., Lee, B. T. K., Wang, Y., & Ruedl, C. (2025) · Science Advances · doi:10.1126/sciadv.adq6038 · Cited by 67 · see citing works
“However, perturbations in microglial activity, often associated with aging, can affect the effective clearance of these neuron-derived A β fibrils, leading to increased plaque formation and the progression of cognitive and behavioral impairments ( 17 – 20 ).”
Changes in Oxidative Damage, Inflammation and [NAD(H)] with Age in Cerebrospinal Fluid
Guest, J., Grant, R., Mori, T. A., & Croft, K. D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085335 · Cited by 66 · see citing works
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 · see citing works
The effect of aged microglia on synaptic impairment and its relevance in neurodegenerative diseases
Triviño, J. J., & von Bernhardi, R. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.104982 · Cited by 43 · see citing works
Muth, C., Schröck, K., Madore, C., Hartmann, K., Fanek, Z., Butovsky, O., Glatzel, M., & Krasemann, S. (2017) · Brain Pathology · doi:10.1111/bpa.12441 · Cited by 23 · see citing works
- Authors
- Njie, E. G., Boelen, E., Stassen, F. R., Steinbusch, H. W. M., Borchelt, D. R., & Streit, W. J.
- Affiliations
- University of Florida (US)
- Maastricht University Medical Centre (NL)
- Corresponding author
- Njie, eMalick G.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 33
- Issue
- 1
- Pages
- 195.e1-195.e12
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC4162517
- OpenAlex
- W2112815582
- Cited by
- 335
- References
- 65
- Citations by year
- 2026: 8 · 2025: 22 · 2024: 14 · 2023: 11 · 2022: 25 · 2021: 29 · 2020: 26 · 2019: 25 · 2018: 25 · 2017: 20 · 2016: 21 · 2015: 14 · 2014: 26 · 2013: 26 · 2012: 20
- FWCI
- 13.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Funders
- NIH Neurobiology of Aging NRSA Training (AG000196-16A1, ROI-NS042775, RO1-AG023665)
- SantaFe HealthCare Alzheimer's Disease Research Center
- “Internationale Stichting Alzheimer Onderzoek (ISAO)”
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- microglia, brain aging, interleukin-6, TNF-α, glutathione, amyloid-beta, phagocytosis, microglial function, Alzheimer's disease, neuroinflammation, aged mice
- MeSH terms
- Aging, Alzheimer Disease, Animals, Brain, Cell Survival, Cells, Cultured, Glutathione, Male, Mice, Inbred C57BL, Phagocytosis, Tumor Necrosis Factor-alpha, Interleukin-6, Amyloid beta-Peptides, Microglia, Mice
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