Lipopolysaccharide-Induced Inflammation Exacerbates Tau Pathology by a Cyclin-Dependent Kinase 5-Mediated Pathway in a Transgenic Model of Alzheimer's Disease
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Inflammation is a critical component of the pathogenesis of Alzheimer's disease (AD). Although not an initiator of this disorder, inflammation nonetheless plays a pivotal role as a driving force that can modulate the neuropathology. Here, we characterized the time course of microglia activation in the brains of a transgenic model of AD (3xTg-AD) and discerned its relationship to the plaque and tangle pathology. We find that microglia became activated in a progressive and age-dependent manner, and this activation correlated with the onset of fibrillar amyloidβ-peptide plaque accumulation and tau hyperphosphorylation. To determine whether microglial activation can exacerbate the pathology, we exposed young 3xTg-AD mice to lipopolysaccharide (LPS), a known inducer of CNS inflammation. Although amyloid precursor protein processing appeared unaffected, we find that LPS significantly induced tau hyperphosphorylation at specific sites that were mediated by the activation of cyclin-dependent kinase 5 (cdk5) through increased formation of the p25 fragment. We further show that administration of roscovitine, a selective and potent inhibitor of cdk5, markedly blocked the LPS-induced tau phosphorylation in the hippocampus. Therefore, this study clearly demonstrates that microglial activation exacerbates key neuropathological features such as tangle formation.
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Promoting microglia activation via LPS- or virus-induced inflammation promotes tau pathology.
“promoting microglia activation via lipopolysaccharide- or virus-induced inflammation promoted tau pathology [187, 304]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [187]
LPS-induced inflammation in mice with amyloidosis or tauopathy increased neuropathology.
“lipopolysaccharide (a major gram negative bacterial cell wall component)-induced inflammation in mice with amyloidosis or tauopathy increased neuropathology [187, 283]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [187]
Pro-inflammatory cytokines released by activated microglia enhance tau pathology through activating tau kinases such as p38 and CDK5.
“Microglia can also indirectly modulate tau pathogenesis through inflammatory pathways; pro-inflammatory cytokines released by activated microglia can enhance tau pathology through activating tau kinases, such as p38 and CDK5 [430, 431].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [431]
Systemic administration of LPS leads to microglial activation in the mouse brain, which results in tau hyperphosphorylation at specific sites.
“Our and other studies found that systemic administration of lipopolysaccharide (LPS, inducer of inflammation) leads to microglial activation in the mouse brain, which results in tau hyperphosphorylation at specific sites [117, 118].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [118]
Chronic intraperitoneal administration of LPS to 3xTg-AD mice for 6 weeks induces marked microglial activation and promotes site-specific tau hyperphosphorylation.
“chronic intraperitoneal administration of LPS to 3xTg-AD mice[G] for 6-weeks is shown to induce marked microglial activation and promote site-specific tau hyperphosphorylation59.”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [59]
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Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Glutamate neurotoxicity and diseases of the nervous system
Choi, D. W. (1988) · Neuron · doi:10.1016/0896-6273(88)90162-6 · Cited by 8,152 · see citing works
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063 · see citing works
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514 · see citing works
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991) · Annals of Neurology · doi:10.1002/ana.410300410 · Cited by 4,397 · see citing works
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126 · see citing works
Self-citationImmunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., et al. (1999) · Nature · doi:10.1038/22124 · Cited by 3,160 · see citing works
Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity
DeKosky, S. T., & Scheff, S. W. (1990) · Annals of Neurology · doi:10.1002/ana.410270502 · Cited by 2,376 · see citing works
Bard, F., Cannon, C., Barbour, R., Burke, R.-L., Games, D., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., et al. (2000) · Nature Medicine · doi:10.1038/78682 · Cited by 2,012 · see citing works
Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease.
Griffin, W. S., Stanley, L. C., Ling, C., White, L., MacLeod, V, Perrot, L. J., White, C. L., & Araoz, C. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.19.7611 · Cited by 1,777 · see citing works
Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration
Patrick, G. N., Zukerberg, L. R., Nikolić, M., de la Monte, S. M., Dikkes, P., & Tsai, L. (1999) · Nature · doi:10.1038/45159 · Cited by 1,541 · see citing works
Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease
Morgan, D., Diamond, D. M., Gottschall, P. E., Ugen, K. E., Dickey, C. A., Hardy, J., Duff, K., Jantzen, P. T., DiCarlo, G., Wilcock, D. M., et al. (2000) · Nature · doi:10.1038/35050116 · Cited by 1,488 · see citing works
Cohen, P., & Frame, S. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35096075 · Cited by 1,478 · see citing works
A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity
Weggen, S., Eriksen, J. L., Das, P., Sagi, S. A., Wang, R., Pietrzik, C. U., Findlay, K. A., Smith, T. E., Murphy, M. P., Bulter, T., et al. (2001) · Nature · doi:10.1038/35102591 · Cited by 1,388 · see citing works
Risk of Alzheimer's disease and duration of NSAID use
Stewart, W. F., Kawas, C., Corrada, M., & Metter, E. J. (1997) · Neurology · doi:10.1212/wnl.48.3.626 · Cited by 1,132 · see citing works
Neurotoxicity induces cleavage of p35 to p25 by calpain
Lee, M.-S., Kwon, Y. T., Li, M., Peng, J., Friedlander, R. M., & Tsai, L. (2000) · Nature · doi:10.1038/35012636 · Cited by 1,057 · see citing works
p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5
Tsai, L., Delalle, I., Caviness, V. S., Chae, T. H., & Harlow, E. (1994) · Nature · doi:10.1038/371419a0 · Cited by 923 · see citing works
Ibuprofen Suppresses Plaque Pathology and Inflammation in a Mouse Model for Alzheimer's Disease
Lim, G. P., Yang, F., Chu, T., Chen, P., Beech, W. K., Teter, B., Tran, T., Ubeda, O. J., Ashe, K. H., Frautschy, S. A., et al. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-15-05709.2000 · Cited by 876 · see citing works
Dickson, D. W., Lee, S. C., Mattiace, L. A., Yen, S.-H. C., & Brosnan, C. F. (1993) · Glia · doi:10.1002/glia.440070113 · Cited by 825 · see citing works
Cruz, J. C., Tseng, H.-C., Goldman, J. A., Shih, H., & Tsai, L.-H. (2003) · Neuron · doi:10.1016/s0896-6273(03)00627-5 · Cited by 609 · 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
Li, Y., Liu, L., Barger, S. W., & Griffin, W. S. T. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-05-01605.2003 · Cited by 563 · see citing works
Interleukin-1 Expression in Different Plaque Types in Alzheimerʼs Disease
Griffin, W. S. T., Sheng, J. G., Roberts, G. W., & Mrak, R. E. (1995) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199503000-00014 · Cited by 546 · see citing works
Cdk5 Is a Key Factor in Tau Aggregation and Tangle Formation In Vivo
Noble, W. J., Olm, V., Takata, K., Casey, E., Mary, O., Meyerson, J. L., Gaynor, K., LaFrancois, J. J., Wang, L., Kondo, T., et al. (2003) · Neuron · doi:10.1016/s0896-6273(03)00259-9 · Cited by 511 · see citing works
Abnormal Alzheimer‐like phosphorylation of tau‐protein by cyclin‐dependent kinases cdk2 and cdk5
Baumann, K., Mandelkow, E., Biernat, J., Piwnica-Worms, H. M., & Mandelkow, E. (1993) · FEBS Letters · doi:10.1016/0014-5793(93)80849-p · Cited by 479 · see citing works
Expression of the histocompatibility glycoprotein HLA-DR in neurological disease
McGeer, P. L., Itagaki, S., & McGeer, E. G. (1988) · Acta Neuropathologica · doi:10.1007/bf00689592 · Cited by 420 · see citing works
Bard, F., Barbour, R., Cannon, C., Carretto, R., Fox, M., Games, D., Guido, T., Hoenow, K., Hu, K., Johnson-Wood, K., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0436286100 · Cited by 411 · see citing works
Sheng, J. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(03)00069-x · Cited by 388 · see citing works
Interleukin-1, neuroinflammation, and Alzheimer's disease
Mrak, R. E. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00287-1 · Cited by 356 · see citing works
Weldon, D. T., Rogers, S. D., Ghilardi, J. R., Finke, M. P., Cleary, J. P., O’Hare, E., Esler, W. P., Maggio, J. E., & Mantyh, P. W. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-06-02161.1998 · Cited by 348 · see citing works
Association of Microglia with Amyloid Plaques in Brains of APP23 Transgenic Mice
Stalder, M., Phinney, A., Probst, A., Sommer, B., Staufenbiel, M., & Jucker, M. (1999) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65423-5 · Cited by 345 · see citing works
Ahlijanian, M. K., Barrezueta, N. X., Williams, R. D., Jakowski, A. B., Kowsz, K. P., McCarthy, S. A., Coskran, T., Carlo, A. A., Seymour, P. A., Burkhardt, J. E., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.040577797 · Cited by 339 · see citing works
Nonsteroidal Anti-Inflammatory Drugs Can Lower Amyloidogenic Aß <sub>42</sub> by Inhibiting Rho
Zhou, Y., Su, Y., Li, B., Liu, F., Ryder, J. W., Wu, X., Gonzalez-DeWhitt, P. A., Gelfanova, V., Hale, J. E., May, P. C., et al. (2003) · Science · doi:10.1126/science.1090154 · Cited by 316 · see citing works
Patrick, G. N., Zhou, P., Kwon, Y. T., Howley, P. M., & Tsai, L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.37.24057 · Cited by 311 · see citing works
Inflammatory responses to amyloidosis in a transgenic mouse model of Alzheimer’s disease
Matsuoka, Y., Picciano, M., Malester, B., LaFrancois, J., Zehr, C., Daeschner, J. M., Olschowka, J. A., Fonseca, M. I., O’Banion, M. K., Tenner, A. J., et al. (2001) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64085-0 · Cited by 303 · see citing works
Savage, M. J., Lin, Y.-G., Ciallella, J. R., Flood, D. G., & Scott, R. W. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03376.2002 · Cited by 291 · see citing works
Apelt, J., & Schliebs, R. (2001) · Brain Research · doi:10.1016/s0006-8993(00)03176-0 · Cited by 289 · see citing works
Brain macrophages synthesize interleukin‐1 and interleukin‐1 mRNAs in vitro
Hetier, E., Ayala‐Sanmartín, J., Denèfle, P., Bousseau, A., Rouget, P., Mallat, M., & Prochiantz, A. (1988) · Journal of Neuroscience Research · doi:10.1002/jnr.490210230 · Cited by 287 · see citing works
Time Course of the Development of Alzheimer-like Pathology in the Doubly Transgenic PS1+APP Mouse
Gordon, M. N., Holcomb, L. A., Jantzen, P. T., DiCarlo, G., Wilcock, D., Boyett, K. W., Connor, K., Melachrino, J., O'Callaghan, J. P., & Morgan, D. (2002) · Experimental Neurology · doi:10.1006/exnr.2001.7754 · Cited by 247 · see citing works
Morphologic association between microglia and senile plaque amyloid in Alzheimer's disease
Perlmutter, L. S., Barron, E., & Chui, H. C. (1990) · Neuroscience Letters · doi:10.1016/0304-3940(90)90748-x · Cited by 240 · see citing works
Inhibition of tau phosphorylating protein kinase cdk5 prevents β‐amyloid‐induced neuronal death
Alvarez, A. R., Toro, R., Cáceres, A., & Maccioni, R. B. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01279-x · Cited by 228 · see citing works
Pei, J.-J., Grundke-Iqbal, I., Iqbal, K., Bogdanovic, N., Winblad, B., & Cowburn, R. F. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00296-0 · Cited by 226 · see citing works
Liu, S. J., Zhang, A. H., Li, H. L., Wang, Q., Deng, H. M., Netzer, W. J., Xu, H., & Wang, J. Z. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02070.x · Cited by 225 · see citing works
Reduced prevalence of AD in users of NSAIDs and H2 receptor antagonists
Anthony, J. C., Breitner, J., Zandi, P., Meyer, M., Jurasová, I., Norton, M., & Stone, S. (2000) · Neurology · doi:10.1212/wnl.54.11.2066 · Cited by 222 · see citing works
Giovannini, M. G., Scali, C., Prosperi, C., Bellucci, A., Vannucchi, M. G., Rosi, S., Pepeu, G., & Casamenti, F. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2002.0538 · Cited by 216 · see citing works
Bellucci, A., Westwood, A. J., Ingram, E., Casamenti, F., Goedert, M., & Spillantini, M. G. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63421-9 · Cited by 215 · see citing works
Huell, M., Strauss, S., Volk, B., Berger, M., & Bauer, J. (1995) · Acta Neuropathologica · doi:10.1007/bf00571510 · Cited by 214 · see citing works
Dringenberg, H. C. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(00)00261-8 · Cited by 191 · see citing works
p39 activates cdk5 in neurons, and is associated with the actin cytoskeleton
Humbert, S., Dhavan, R., & Tsai, L. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.6.975 · Cited by 188 · see citing works
Sheng, J. G., Jones, R. A., Zhou, X. Q., McGinness, J. M., Van Eldik, L. J., Mrak, R. E., & Griffin, W. S. T. (2001) · Neurochemistry International · doi:10.1016/s0197-0186(01)00041-9 · Cited by 176 · see citing works
Atzori, C., Ghetti, B. F., Piva, R., Srinivasan, A., Zolo, P., Delisle, M. B., Mirra, S. S., & Migheli, A. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.12.1190 · Cited by 175 · see citing works
Griffin, W. S. T., Sheng, J. G., Gentleman, S. M., Graham, D. I., Mrak, R. E., & Roberts, G. W. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90066-3 · Cited by 170 · see citing works
Anti-inflammatory Drugs Protect Against Alzheimer Disease at Low Doses
Broe, G. A., Grayson, D. A., Creasey, H. M., Waite, L. M., Casey, B. J., Bennett, H. P., Brooks, W. S., & Halliday, G. M. (2000) · Archives of Neurology · doi:10.1001/archneur.57.11.1586 · Cited by 160 · see citing works
Frautschy, S. A., Cole, G. M., & Baird, A. (1992) · PubMed Central · Cited by 157 · see citing works
EVANS, D. B., Rank, K. B., Bhattacharya, K., Thomsen, D. R., Gurney, M. E., & Sharma, S. K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000808200 · Cited by 155 · see citing works
(1998) · Europe PMC (PubMed Central) · Cited by 146 · see citing works
Lynch, A. M., Walsh, C., Delaney, A., Nolan, Y. M., Campbell, V. A., & Lynch, M. A. (2004) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02157.x · Cited by 145 · see citing works
Grammas, P., & Ovase, R. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)61105-4 · Cited by 134 · see citing works
Glycogen Synthase Kinase-3β Is Complexed with Tau Protein in Brain Microtubules
Sun, W., Qureshi, H. Y., Cafferty, P. W., Sobue, K., Agarwal-Mawal, A., Neufield, K. D., & Paudel, H. K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m107182200 · Cited by 110 · see citing works
Ishiguro, K., Omori, A., Sato, K., Tomizawa, K., Imahori, K., & Uchida, T. (1991) · Neuroscience Letters · doi:10.1016/0304-3940(91)90259-v · Cited by 106 · see citing works
Cdk5: One of the links between senile plaques and neurofibrillary tangles?
Lee, M.-S., & Tsai, L. (2003) · Journal of Alzheimer s Disease · doi:10.3233/jad-2003-5207 · Cited by 104 · see citing works
Zhang, M., Li, J., Chakrabarty, P., et al. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63347-0 · Cited by 102 · see citing works
Lund, E. T., McKenna, R., EVANS, D. B., Sharma, S. K., & Mathews, W. R. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00130.x · Cited by 74 · see citing works
Augustinack, J. C., Sanders, J. L., Tsai, L., & Hyman, B. T. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.6.557 · Cited by 72 · see citing works
Sasaki, A., Shoji, M., Harigaya, Y., Kawarabayashi, T., Ikeda, M., Naito, M., Matsubara, E., Abe, K., & Nakazato, Y. (2002) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-002-0643-8 · Cited by 61 · see citing works
Shelton, S. B., Krishnamurthy, P., & Johnson, G. V. W. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20051 · Cited by 26 · see citing works
IL-1β and IL-6 in mouse parotid acinar cells: characterization of synthesis, storage, and release
Tanda, N., Ohyama, H., Yamakawa, M., Ericsson, M., Tsuji, T., McBride, J., Elovic, A., Wong, D. T., & Login, G. R. (1998) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1998.274.1.g147 · Cited by 24 · see citing works
Holmlund, L., Toro, V. C., & Iverfeldt, K. (2002) · International Journal of Molecular Medicine · doi:10.3892/ijmm.10.3.245 · Cited by 8 · see citing works
(2002) · Journal of Nursing Management · doi:10.1046/j.1365-2834.2002.00335.x · Cited by 3 · see citing works
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Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208 · see citing works
Inflammation as a central mechanism in Alzheimer's disease
Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.06.014 · Cited by 2,253 · see citing works
Gut microbiome alterations in Alzheimer’s disease
Vogt, N. M., Kerby, R. L., Dill-McFarland, K. A., Harding, S. J., Merluzzi, A. P., Johnson, S. C., Carlsson, C. M., Asthana, S., Zetterberg, H., Blennow, K., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-13601-y · Cited by 2,137 · see citing works
Innate immune activation in neurodegenerative disease
Heneka, M. T., Kummer, M. P., & Latz, E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3705 · Cited by 1,437 · see citing works
Microglial priming in neurodegenerative disease
Perry, V. H., & Holmes, C. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.38 · Cited by 1,127 · see citing works
Wyss-Coray (2006) · doi:10.1038/nm1484 · Cited by 1,284 · see citing works
Manczak, M., Anekonda, T. S., Henson, E., Park, B. S., Quinn, J., & Reddy, P. H. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl066 · Cited by 1,104 · see citing works
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994 · see citing works
The cholinergic system in aging and neuronal degeneration
Schliebs, R., & Arendt, T. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.11.058 · Cited by 1,047 · see citing works
Systemic infections and inflammation affect chronic neurodegeneration
Perry, V. H., Cunningham, C., & Holmes, C. (2007) · Nature Reviews Immunology · doi:10.1038/nri2015 · Cited by 1,027 · see citing works
Innate immunity in Alzheimer's disease
Heneka, M. T., Golenbock, D. T., & Latz, E. (2015) · Nature Immunology · doi:10.1038/ni.3102 · Cited by 902 · see citing works
Cogswell, J. P., Ward, J., Taylor, I. A., Waters, M., Shi, Y., Cannon, B., Kelnar, K., Kemppainen, J., Brown, D., Chen, C., et al. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14103 · Cited by 943 · see citing works
Molecular Interplay between Mammalian Target of Rapamycin (mTOR), Amyloid-β, and Tau
Caccamo, A., Majumder, S., Richardson, A., Strong, R., & Oddo, S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.100420 · Cited by 881 · see citing works
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Cunningham, C. (2013) · Glia · doi:10.1002/glia.22350 · Cited by 769 · see citing works
Does neuroinflammation fan the flame in neurodegenerative diseases?
Frank-Cannon, T. C., Alto, L. T., McAlpine, F. E., & Tansey, M. G. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-47 · Cited by 751 · see citing works
Spangenberg, E. E., Lee, R. J., Najafi, A. R., Rice, R. A., Elmore, M. R. P., Blurton-Jones, M., West, B. L., & Green, K. N. (2016) · Brain · doi:10.1093/brain/aww016 · Cited by 700 · see citing works
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Bhaskar, K., Konerth, M., Kokiko-Cochran, O. N., Cardona, A., Ransohoff, R. M., & Lamb, B. T. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.023 · Cited by 639 · see citing works
Nagpal, R., Neth, B. J., Wang, S., Craft, S., & Yadav, H. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.08.032 · Cited by 653 · see citing works
Maphis, N., Xu, G., Kokiko-Cochran, O. N., Jiang, S., Cardona, A., Ransohoff, R. M., Lamb, B. T., & Bhaskar, K. (2015) · Brain · doi:10.1093/brain/awv081 · Cited by 595 · see citing works
Glucocorticoids increase amyloid-β and tau pathology in a mouse model of alzheimer’s disease
Green, K. N., Billings, L. M., Roozendaal, B., McGaugh, J. L., & LaFerla, F. M. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2797-06.2006 · Cited by 623 · see citing works
Self-citationKim, M.-S., Kim, Y., Choi, H., Kim, W., Park, S., Lee, D., Kim, D. K., Kim, H. J., Choi, H., Hyun, D.-W., et al. (2020) · Gut · doi:10.1136/gutjnl-2018-317431 · Cited by 614 · see citing works
Cunningham, C., Campion, S., Lunnon, K., Murray, C. L., Woods, J. F. C., Deacon, R. M. J., Rawlins, J. N. P., & Perry, V. H. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.07.024 · Cited by 584 · see citing works
Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight
Shi, Y., & Holtzman, D. M. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0051-1 · Cited by 595 · see citing works
The role of interleukin-1 in neuroinflammation and Alzheimer disease: an evolving perspective
Shaftel, S. S., Griffin, W. S. T., & O'Banion, M. K. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-7 · Cited by 565 · see citing works
Lipopolysaccharide-induced neuroinflammation as a bridge to understand neurodegeneration
Batista, C. R. A., Gomes, G. F., Candelario-Jalil, E., Fiebich, B. L., & de Oliveira, A. C. P. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092293 · Cited by 529 · see citing works
Cribbs, D. H., Berchtold, N. C., Perreau, V., Coleman, P. D., Rogers, J., Tenner, A. J., & Cotman, C. W. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-179 · Cited by 499 · 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
“Our and other studies found that systemic administration of lipopolysaccharide (LPS, inducer of inflammation) leads to microglial activation in the mouse brain, which results in tau hyperphosphorylation at specific sites [117, 118].”
Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model
Shi, Y., Manis, M., Long, J., Wang, K., Sullivan, P. M., Remolina Serrano, J., Hoyle, R., & Holtzman, D. M. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20190980 · Cited by 448 · see citing works
Kitazawa, 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
Self-citationStancu, I.-C., Cremers, N., Vanrusselt, H., Couturier, J., Vanoosthuyse, A., Kessels, S., Lodder, C., Brône, B., Huaux, F., Octave, J.-N., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-018-01957-y · Cited by 447 · see citing works
Animal Models of Alzheimer Disease
LaFerla, F. M., & Green, K. N. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006320 · Cited by 419 · see citing works
Self-citationGlial contributions to neurodegeneration in tauopathies
Leyns, C. E. G., & Holtzman, D. M. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0192-x · Cited by 409 · see citing works
Neuroinflammatory 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
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
Self-citationTLR4 Cross-Talk With NLRP3 Inflammasome and Complement Signaling Pathways in Alzheimer's Disease
Yang, J., Wise, L., & Fukuchi, K.-I. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00724 · Cited by 387 · see citing works
Review: Systemic inflammation and<scp>A</scp>lzheimer's disease
Holmes, C. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2012.01307.x · Cited by 356 · see citing works
Tau and neuroinflammation: what impact for Alzheimer's disease and tauopathies?
Laurent, C., Buée, L., & Blum, D. (2018) · Biomedical Journal · doi:10.1016/j.bj.2018.01.003 · Cited by 348 · see citing works
High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model
Julien, C., Tremblay, C., Phivilay, A., Berthiaume, L., Émond, V., Julien, P., & Calon, F. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.08.022 · Cited by 288 · see citing works
Microglia 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
LPS- induced inflammation exacerbates phospho-tau pathology in rTg4510 mice
Lee, D. C., Rizer, J., Selenica, M.-L. B., Reid, P., Kraft, C., Johnson, A., Blair, L., Gordon, M. N., Dickey, C. A., & Morgan, D. (2010) · Journal of Neuroinflammation · doi:10.1186/1742-2094-7-56 · Cited by 293 · see citing works
Westin, K., Buchhave, P., Nielsen, H., Minthon, L., Janciauskiene, S., & Hansson, O. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030525 · Cited by 277 · see citing works
Janelsins, M. C., Mastrangelo, M. A., Oddo, S., LaFerla, F. M., Federoff, H. J., & Bowers, W. J. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-23 · Cited by 260 · see citing works
Self-citationThe olfactory bulb as the entry site for prion-like propagation in neurodegenerative diseases
Rey, N. L., Wesson, D. W., & Brundin, P. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.12.013 · Cited by 257 · see citing works
Aging‐dependent changes of microglial cells and their relevance for neurodegenerative disorders
Von Bernhardi, R., Tichauer, J. E., & Eugenín, J. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06537.x · Cited by 258 · see citing works
Davis, D. H. J., Muniz-Terrera, G., Keage, H. A. D., Stephan, B. C. M., Fleming, J., Ince, P. G., Matthews, F. E., Cunningham, C., Ely, E. W., MacLullich, A. M. J., et al. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.3423 · Cited by 252 · see citing works
Dual Roles for Perivascular Macrophages in Immune-to-Brain Signaling
Serrats, J., Schiltz, J. C., García-Bueno, B., van Rooijen, N., Reyes, T. M., & Sawchenko, P. E. (2010) · Neuron · doi:10.1016/j.neuron.2009.11.032 · Cited by 253 · see citing works
Clayton, K., Delpech, J. C., Herron, S., Iwahara, N., Ericsson, M., Saito, T., Saido, T. C., Ikezu, S., & Ikezu, T. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00440-9 · Cited by 245 · see citing works
Enhanced tau aggregation in the presence of Amyloid β
Bennett, R. E., DeVos, S. L., Dujardin, S., Corjuc, B., Gor, R., Gonzalez, J., Roe, A. D., Frosch, M. P., Pitstick, R., Carlson, G. A., et al. (2017) · The American Journal of Pathology · doi:10.1016/j.ajpath.2017.03.011 · Cited by 245 · see citing works
Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies
Sinsky, J., Pichlerova, K., & Hanes, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179207 · Cited by 220 · see citing works
Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function
Spiteri, A. G., Wishart, C. L., Pamphlett, R., Locatelli, G., & King, N. J. C. (2022) · Acta Neuropathologica · doi:10.1007/s00401-021-02384-2 · Cited by 216 · see citing works
“Indeed, lipopolysaccharide (a major gram negative bacterial cell wall component)-induced inflammation in mice with amyloidosis or tauopathy increased neuropathology [187, 283].”
BackgroundIntersection of pathological tau and microglia at the synapse
Vogels, T., Murgoci, A.-N., & Hromádka, T. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0754-y · Cited by 197 · see citing works
Cunningham, C., & Hennessy, E. (2015) · Alzheimer's Research & Therapy · doi:10.1186/s13195-015-0117-2 · Cited by 211 · see citing works
Inflammation Induced by Infection Potentiates Tau Pathological Features in Transgenic Mice
Sy, M., Kitazawa, M., Medeiros, R., Whitman, L., Cheng, D., Lane, T. E., & LaFerla, F. M. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.02.012 · Cited by 210 · see citing works
Self-citationKitazawa, M., Medeiros, R., & M. LaFerla, F. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212799315786 · Cited by 178 · see citing works
Efficacy and safety of immunization with phosphorylated tau against neurofibrillary tangles in mice
Boimel, M., Grigoriadis, N., Lourbopoulos, A., Haber, E., Abramsky, O., & Rosenmann, H. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.05.010 · Cited by 174 · see citing works
Kitazawa, M., Cheng, D., & LaFerla, F. M. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05901.x · Cited by 165 · see citing works
Self-citationBasheer, N., Smolek, T., Hassan, I., Liu, F., Iqbal, K., Zilka, N., & Novak, P. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02113-z · Cited by 159 · see citing works
Neuroinflammation, gut microbiome, and Alzheimer's disease
Lin, L., Zheng, L. J., & Zhang, L. J. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0983-2 · Cited by 147 · see citing works
Systemic inflammation and delirium: important co-factors in the progression of dementia
Cunningham, C. (2011) · Biochemical Society Transactions · doi:10.1042/bst0390945 · Cited by 153 · see citing works
Markers of neuroinflammation associated with Alzheimer’s disease pathology in older adults
Popp, J., Oikonomidi, A., Tautvydaitė, D., Dayon, L., Bacher, M., Migliavacca, E., Henry, H., Kirkland, R., Severin, I., Wojcik, J., et al. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2017.01.020 · Cited by 136 · see citing works
Zhou, J., Yu, W., Zhang, M., Tian, X., Li, Y., & Lü, Y. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02748-x · Cited by 139 · see citing works
PK11195 labels activated microglia in Alzheimer's disease and in vivo in a mouse model using PET
Venneti, S., Lopresti, B. J., Wang, G., Hamilton, R. L., Mathis, C. A., Klunk, W. E., Apte, U. M., & Wiley, C. A. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.11.005 · Cited by 138 · see citing works
The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease
Kokiko-Cochran, O. N., & Godbout, J. P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00672 · Cited by 128 · 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
Targeting innate immunity for neurodegenerative disorders of the central nervous system
Andreasson, K. I., Bachstetter, A. D., Colonna, M., Ginhoux, F., Holmes, C., Lamb, B., Landreth, G., Lee, D. C., Low, D., Lynch, M. A., et al. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13667 · Cited by 126 · see citing works
Mastrangelo, M. A., Sudol, K. L., Narrow, W. C., & Bowers, W. J. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.090059 · Cited by 100 · see citing works
Johansson, J. U., Pradhan, S., Lokteva, L. A., Woodling, N. S., Ko, N., Brown, H. D., Wang, Q., Loh, C., Cekanaviciute, E., Buckwalter, M., et al. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.2203-13.2013 · Cited by 96 · see citing works
Larouche, E., Hudon, C., & Goulet, S. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.05.058 · Cited by 93 · see citing works
Of microbes and minds: A narrative review on the second brain aging
Calvani, R., Picca, A., Lo Monaco, M. R., Landi, F., Bernabei, R., & Marzetti, E. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00053 · Cited by 92 · see citing works
Loss of tau rescues inflammation-mediated neurodegeneration
Maphis, N., Xu, G., Kokiko-Cochran, O. N., Cardona, A. E., Ransohoff, R. M., Lamb, B. T., & Bhaskar, K. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00196 · Cited by 91 · see citing works
Qin, Y., Liu, Y., Hao, W., Decker, Y., Tomic, I., Menger, M. D., Liu, C., & Fassbender, K. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600873 · Cited by 90 · see citing works
Cook, C., Kang, S. S., Carlomagno, Y., Lin, W.-L., Yue, M., Kurti, A., Shinohara, M., Jansen-West, K., Perkerson, E., Castanedes-Casey, M., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv336 · Cited by 82 · see citing works
Hoeijmakers, L., Heinen, Y., van Dam, A.-M., Lucassen, P. J., & Korosi, A. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00398 · Cited by 85 · see citing works
Simon, E., Obst, J., & Gomez-Nicola, D. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2018.01.059 · Cited by 83 · see citing works
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 · see citing works
Mapping neuroinflammation in frontotemporal dementia with molecular PET imaging
Zhang, J. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0236-5 · Cited by 62 · see citing works
Suppression of LPS-induced tau hyperphosphorylation by serum amyloid A
Liu, J., Wang, D., Li, S.-Q., Yu, Y., & Ye, R. D. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0493-y · Cited by 58 · see citing works
Lee, D. C., Rizer, J., Hunt, J. B., Selenica, M. ‐. B., Gordon, M. N., & Morgan, D. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12002 · Cited by 57 · see citing works
McClure, R., Ong, H., Janve, V., Barton, S., Zhu, M., Li, B., Dawes, M., Jerome, W. G., Anderson, A., Massion, P., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160289 · Cited by 54 · see citing works
Expression of Tau40 Induces Activation of Cultured Rat Microglial Cells
Wang, L., Jiang, Q., Chu, J., Lin, L., Li, X.-G., Chai, G.-S., Wang, Q., Wang, J.-Z., & Tian, Q. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076057 · Cited by 47 · see citing works
Giannopoulos, P. F., Chu, J., Sperow, M., Li, J.-G., Yu, W. H., Kirby, L. G., Abood, M., & Praticò, D. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.01.015 · Cited by 48 · see citing works
RetractedMcFarland, K. N., & Chakrabarty, P. (2022) · Neurotherapeutics · doi:10.1007/s13311-021-01179-3 · Cited by 48 · see citing works
Britschgi, M., Takeda-Uchimura, Y., Rockenstein, E., Johns, H., Masliah, E., & Wyss-Coray, T. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-220 · Cited by 45 · see citing works
Andreadou, E. G., Katsipis, G., Tsolaki, M., & Pantazaki, A. A. (2021) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2021.577561 · Cited by 31 · see citing works
Gardner, L. E., White, J. D., Eimerbrink, M. J., Boehm, G. W., & Chumley, M. J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.06.007 · Cited by 29 · see citing works
Adler, D. A., Ammanuel, S., Lei, J., Dada, T., Borbiev, T., Johnston, M. V., Kadam, S. D., & Burd, I. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.06.022 · Cited by 22 · see citing works
Grathwohl, S., Quansah, E., Maroof, N., Steiner, J. A., Spycher, L., Benmansour, F., Duran-Pacheco, G., Siebourg-Polster, J., Oroszlan-Szovik, K., Remy, H., et al. (2020) · doi:10.21203/rs.3.rs-100199/v1 · Cited by 17 · see citing works
Bazan, N. G. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8897-0 · Cited by 15 · see citing works
Daulatzai, M. A. (2015) · Neurotoxicity Research · doi:10.1007/s12640-015-9528-x · Cited by 12 · see citing works
- Authors
- Kitazawa, M., Oddo, S., Yamasaki, T. R., Green, K. N., & LaFerla, F. M.
- Affiliations
- University of California, Irvine (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-09-28
- Volume
- 25
- Issue
- 39
- Pages
- 8843-8853
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6725603
- OpenAlex
- W1976445933
- Cited by
- 697
- References
- 69
- Citations by year
- 2026: 23 · 2025: 27 · 2024: 38 · 2023: 34 · 2022: 28 · 2021: 56 · 2020: 36 · 2019: 30 · 2018: 44 · 2017: 26 · 2016: 36 · 2015: 47 · 2014: 47 · 2013: 33 · 2012: 42
- FWCI
- 14.18
- 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
- Alzheimer's Association
- National Institutes of Health
- National Institute on Aging (AG0212982, AG17968, R01AG017968)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, lipopolysaccharide, neuroinflammation, microglial activation, tau hyperphosphorylation, cyclin-dependent kinase 5, roscovitine, amyloid plaques, neurofibrillary tangles, 3xTg-AD mice, hippocampus, APP processing
- MeSH terms
- Roscovitine, Aging, Alzheimer Disease, Animals, Disease Models, Animal, Encephalitis, Enzyme Activation, Female, Hippocampus, Lipopolysaccharides, Male, Mice, Transgenic, Neural Pathways, Phosphorylation, Purines, tau Proteins, Microglia, Tauopathies, Protein Kinase Inhibitors, Cyclin-Dependent Kinase 5, Mice
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