Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice
Open accessAbstract
BACKGROUND: Inflammation is suspected to contribute to the progression and severity of neurodegeneration in Alzheimer's disease (AD). Transgenic mice overexpressing the london mutant of amyloid precursor protein, APP [V717I], robustly recapitulate the amyloid pathology of AD. METHODS: Early and late, temporal and spatial characteristics of inflammation were studied in APP [V717I] mice at 3 and 16 month of age. Glial activation and expression of inflammatory markers were determined by immunohistochemistry and RT-PCR. Amyloid deposition was assessed by immunohistochemistry, thioflavine S staining and western blot experiments. BACE1 activity was detected in brain lysates and in situ using the BACE1 activity kit from R&D Systems, Wiesbaden, Germany. RESULTS: Foci of activated micro- and astroglia were already detected at age 3 months, before any amyloid deposition. Inflammation parameters comprised increased mRNA levels coding for interleukin-1beta, interleukin-6, major histocompatibility complex II and macrophage-colony-stimulating-factor-receptor. Foci of CD11b-positive microglia expressed these cytokines and were neighbored by activated astrocytes. Remarkably, beta-secretase (BACE1) mRNA, neuronal BACE1 protein at sites of focal inflammation and total BACE1 enzyme activity were increased in 3 month old APP transgenic mice, relative to age-matched non-transgenic mice. In aged APP transgenic mice, the mRNA of all inflammatory markers analysed was increased, accompanied by astroglial iNOS expression and NO-dependent peroxynitrite release, and with glial activation near almost all diffuse and senile Abeta deposits. CONCLUSION: The early and focal glial activation, in conjunction with upregulated BACE1 mRNA, protein and activity in the presence of its substrate APP, is proposed to represent the earliest sites of amyloid deposition, likely evolving into amyloid plaques.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CCL2 and TNFα mRNA levels were elevated in APPPS1;Cx3cr1+/+ mouse brain.
“Similar to previous findings in AD brains and mouse models, 39 -42 the levels of CCL2 and TNF␣ mRNAs were elevated in the APPPS1;Cx3cr1 ϩ/ϩ mouse brain.”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [41]
The citation supports the sentence’s reference to previous inflammatory findings in AD mouse models: the Discussion reports TNFα mRNA in an earlier APP-transgenic mouse study. It does not support elevated CCL2 mRNA, and its own Results say TNFα was undetectable in APP[V717I] mice. The APPPS1;Cx3cr1+/+ result is the citing authors’ finding, not one attributed to this source. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPrevious studies of our group have identified molecular differences between SAD and FAD in addition to divergences in clinical manifestations.
“Previous studies of our group have identified molecular differences between SAD and FAD [55, 56, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79] in addition to divergences in the clinical manifestations [55, 56].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [71]
The Background (page unavailable) links familial Alzheimer’s disease to APP mutations, and the Conclusion (page unavailable) reports increased BACE1 expression and activity in mice carrying a mutant APP gene. The paper does not compare sporadic and familial Alzheimer’s disease or establish molecular differences between them; the clinical-manifestations clause is attributed to other citations. (LLM, conf=0.78)
Experimental — accuracy not yet measuredFine‐tuned modification of astrocytic GFAP and vimentin expression is critical for the execution of the astrocyte reactive program.
“fine‐tuned modification of astrocytic GFAP and vimentin expression is critical for the execution of the astrocyte reactive program [28, 71, 91].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [71]
The Results and Discussion (page unavailable) associate increased astrocytic GFAP expression with activation in APP[V717I] mice. They do not address vimentin or establish that fine-tuned changes in either protein are critical for executing a reactive program. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAstroglial proliferation has also been related with GFAP upregulation.
“Astroglial proliferation has also been related with GFAP upregulation [71, 91, 110].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [71]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Immunization 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
Amyloid deposition as the central event in the aetiology of Alzheimer’s disease
Hardy, J., & Allsop, D. (1991) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(91)90609-v · Cited by 2,538 · see citing works
Nonsteroidal Antiinflammatory Drugs and the Risk of Alzheimer's Disease
in 't Veld, B. A., Ruitenberg, A., Hofman, A., Launer, L. J., van Duijn, C. M., Stijnen, T., Breteler, M. M. B., & Stricker, B. H. C. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa010178 · Cited by 1,196 · cited 1× · see citing works
“long term medication with non-steroidal anti-inflammatory drugs (NSAIDs) appears to decrease the risk, delay the onset and slow the cognitive decline of AD patients [15-17].”
McGeer, P. L., Itagaki, S., Tago, H., & McGeer, E. G. (1987) · Neuroscience Letters · doi:10.1016/0304-3940(87)90696-3 · Cited by 836 · see citing works
Murray, C. A., & Lynch, M. A. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-08-02974.1998 · Cited by 359 · see citing works
Flagged first, then by citations
Research works printed but not linked: 32
- Dingwall C Spotlight on BACE: the secretases as targets for treatment in Alzheimer disease J Clin Invest 2001 108 1243 1246 11696563 10.1172/JCI200114402 PMC209454 · DOI
- Esler WP Wolfe MS A portrait of Alzheimer secretases--new features and familiar faces Science 2001 293 1449 1454 11520976 10.1126/science.1064638 · DOI · Paper page
- Hsiao K Chapman P Nilsen S Eckman C Harigaya Y Younkin S Yang F Cole G Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice Science 1996 274 99 102 8810256 10.1126/science.274.5284.99 · DOI · Paper page
- Sturchler-Pierrat C Abramowski D Duke M Wiederhold KH Mistl C Rothacher S Ledermann B Burki K Frey P Paganetti PA Waridel C Calhoun ME Jucker M Probst A Staufenbiel M Sommer B Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology Proc Natl Acad Sci U S A 1997 94 13287 13292 9371838 10.1073/pnas.94.24.13287 PMC24301 · DOI · Paper page
- Moechars D Dewachter I Lorent K Reverse D Baekelandt V Naidu A Tesseur I Spittaels K Haute CV Checler F Godaux E Cordell B Van Leuven F Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain J Biol Chem 1999 274 6483 6492 10037741 10.1074/jbc.274.10.6483 · DOI · Paper page
- Van Dorpe J Smeijers L Dewachter I Nuyens D Spittaels K Van Den HC Mercken M Moechars D Laenen I Kuiperi C Bruynseels K Tesseur I Loos R Vanderstichele H Checler F Sciot R Van Leuven F Prominent cerebral amyloid angiopathy in transgenic mice overexpressing the london mutant of human APP in neurons Am J Pathol 2000 157 1283 1298 11021833 PMC1850171
- Lamb BT Bardel KA Kulnane LS Anderson JJ Holtz G Wagner SL Sisodia SS Hoeger EJ Amyloid production and deposition in mutant amyloid precursor protein and presenilin-1 yeast artificial chromosome transgenic mice Nat Neurosci 1999 2 695 697 10412057 10.1038/11154 · DOI
- Eikelenboom P van Gool WA Neuroinflammatory perspectives on the two faces of Alzheimer's disease J Neural Transm 2004 111 281 294 14991455 10.1007/s00702-003-0055-1 · DOI
- Akiyama H Barger S Barnum S Bradt B Bauer J Cole GM Cooper NR Eikelenboom P Emmerling M Fiebich BL Finch CE Frautschy S Griffin WS Hampel H Hull M Landreth G Lue L Mrak R Mackenzie IR McGeer PL O'Banion MK Pachter J Pasinetti G Plata-Salaman C Rogers J Rydel R Shen Y Streit W Strohmeyer R Tooyoma I Van Muiswinkel FL Veerhuis R Walker D Webster S Wegrzyniak B Wenk G Wyss-Coray T Inflammation and Alzheimer's disease Neurobiol Aging 2000 21 383 421 10858586 10.1016/S0197-4580(00)00124-X PMC3887148 · DOI · Paper page
- Nicoll JA Mrak RE Graham DI Stewart J Wilcock G MacGowan S Esiri MM Murray LS Dewar D Love S Moss T Griffin WS Association of interleukin-1 gene polymorphisms with Alzheimer's disease Ann Neurol 2000 47 365 368 10716257 10.1002/1531-8249(200003)47:3<365::AID-ANA13>3.0.CO;2-G PMC3833599 · DOI
- Papassotiropoulos A Bagli M Jessen F Bayer TA Maier W Rao ML Heun R A genetic variation of the inflammatory cytokine interleukin-6 delays the initial onset and reduces the risk for sporadic Alzheimer's disease Ann Neurol 1999 45 666 668 10319892 10.1002/1531-8249(199905)45:5<666::AID-ANA18>3.0.CO;2-3 · DOI
- McCusker SM Curran MD Dynan KB McCullagh CD Urquhart DD Middleton D Patterson CC McIlroy SP Passmore AP Association between polymorphism in regulatory region of gene encoding tumour necrosis factor alpha and risk of Alzheimer's disease and vascular dementia: a case-control study Lancet 2001 357 436 439 11273064 10.1016/S0140-6736(00)04008-3 · DOI
- Rogers J Kirby LC Hempelman SR Berry DL McGeer PL Kaszniak AW Zalinski J Cofield M Mansukhani L Willson P. Clinical trial of indomethacin in Alzheimer's disease Neurology 1993 43 1609 1611 8351023
- McGeer PL Schulzer M McGeer EG Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies Neurology 1996 47 425 432 8757015
- Sastre M Dewachter I Landreth GE Willson TM Klockgether T Van Leuven F Heneka MT Nonsteroidal anti-inflammatory drugs and peroxisome proliferator-activated receptor-gamma agonists modulate immunostimulated processing of amyloid precursor protein through regulation of beta-secretase J Neurosci 2003 23 9796 9804 14586007 PMC6740896
- Lim GP Yang F Chu T Chen P Beech W Teter B Tran T Ubeda O Ashe KH Frautschy SA Cole GM Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease J Neurosci 2000 20 5709 5714 10908610 PMC6772529
- Fluhrer R Multhaup G Schlicksupp A Okochi M Takeda M Lammich S Willem M Westmeyer G Bode W Walter J Haass C Identification of a beta-secretase activity, which truncates amyloid beta-peptide after its presenilin-dependent generation Journal of Biological Chemistry 2003 278 5531 5538 12471021 10.1074/jbc.M211485200 · DOI
- Rossner S Apelt J Schliebs R Perez-Polo JR Bigl V Neuronal and glial beta-secretase (BACE) protein expression in transgenic Tg2576 mice with amyloid plaque pathology J Neurosci Res 2001 64 437 446 11391698 10.1002/jnr.1095 · DOI
- Barger SW Harmon AD Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E Nature 1997 388 878 881 9278049 10.1038/42257 · DOI · Paper page
- Blasko I Marx F Steiner E Hartmann T Grubeck-Loebenstein B TNFalpha plus IFNgamma induce the production of Alzheimer beta-amyloid peptides and decrease the secretion of APPs FASEB J 1999 13 63 68 9872930
- Mehlhorn G Hollborn M Schliebs R Induction of cytokines in glial cells surrounding cortical beta-amyloid plaques in transgenic Tg2576 mice with Alzheimer pathology Int J Dev Neurosci 2000 18 423 431 10817926 10.1016/S0736-5748(00)00012-5 · DOI
- Sly LM Krzesicki RF Brashler JR Buhl AE McKinley DD Carter DB Chin JE Endogenous brain cytokine mRNA and inflammatory responses to lipopolysaccharide are elevated in the Tg2576 transgenic mouse model of Alzheimer's disease Brain Res Bull 2001 56 581 588 11786245 10.1016/S0361-9230(01)00730-4 · DOI
- Abbas N Bednar I Mix E Marie S Paterson D Ljungberg A Morris C Winblad B Nordberg A Zhu J Up-regulation of the inflammatory cytokines IFN-gamma and IL-12 and down-regulation of IL-4 in cerebral cortex regions of APP(SWE) transgenic mice J Neuroimmunol 2002 126 50 57 12020956 10.1016/S0165-5728(02)00050-4 · DOI
- Benzing WC Wujek JR Ward EK Shaffer D Ashe KH Younkin SG Brunden KR Evidence for glial-mediated inflammation in aged APP(SW) transgenic mice Neurobiol Aging 1999 20 581 589 10674423 10.1016/S0197-4580(99)00065-2 · DOI
- Apelt J Schliebs R Beta-amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology Brain Res 2001 894 21 30 11245811 10.1016/S0006-8993(00)03176-0 · DOI
- Szczepanik AM Rampe D Ringheim GE Amyloid-beta peptide fragments p3 and p4 induce pro-inflammatory cytokine and chemokine production in vitro and in vivo J Neurochem 2001 77 304 317 11279286
- Tancredi V D'Antuono M Cafe C Giovedi S Bue MC D'Arcangelo G Onofri F Benfenati F The inhibitory effects of interleukin-6 on synaptic plasticity in the rat hippocampus are associated with an inhibition of mitogen-activated protein kinase ERK J Neurochem 2000 75 634 643 10899938 10.1046/j.1471-4159.2000.0750634.x · DOI
- Graber HU Zurbriggen A Vandevelde M Identification of canine glial cells by nonradioactive in situ hybridization Zentralbl Veterinarmed A 1993 40 665 671 8135072
- Vodovotz Y Lucia MS Flanders KC Chesler L Xie QW Smith TW Weidner J Mumford R Webber R Nathan C Roberts AB Lippa CF Sporn MB Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease J Exp Med 1996 184 1425 1433 8879214 10.1084/jem.184.4.1425 PMC2192831 · DOI
- Smith MA Richey Harris PL Sayre LM Beckman JS Perry G Widespread peroxynitrite-mediated damage in Alzheimer's disease J Neurosci 1997 17 2653 2657 9092586 PMC6573097
- Bigl M Apelt J Luschekina EA Lange-Dohna C Rossner S Schliebs R Expression of beta-secretase mRNA in transgenic Tg2576 mouse brain with Alzheimer plaque pathology Neurosci Lett 2000 292 107 110 10998560 10.1016/S0304-3940(00)01452-X · DOI
- Irizarry MC Locascio JJ Hyman BT beta-site APP cleaving enzyme mRNA expression in APP transgenic mice: anatomical overlap with transgene expression and static levels with aging Am J Pathol 2001 158 173 177 11141490 PMC1850271
Cited by
Sorted by citations
Immune attack: the role of inflammation in Alzheimer disease
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3880 · Cited by 2,134 · see citing works
The Cellular Phase of Alzheimer’s Disease
De Strooper, B., & Karran, E. (2016) · Cell · doi:10.1016/j.cell.2015.12.056 · Cited by 1,990 · see citing works
Wyss-Coray (2006) · doi:10.1038/nm1484 · Cited by 1,284 · 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
Self-citationMicroglia, 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
Pivotal role of TLR4 receptors in alcohol-induced neuroinflammation and brain damage
Alfonso-Loeches, S., Pascual-Lucas, M., Blanco, A. M., Sanchez-Vera, I., & Guerri, C. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0976-10.2010 · Cited by 579 · see citing works
Glial cells in (patho)physiology
Parpura, V., Heneka, M. T., Montana, V., Oliet, S. H. R., Schousboe, A., Haydon, P. G., Stout, R. F., Spray, D. C., Reichenbach, A., Pannicke, T., et al. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07664.x · Cited by 561 · see citing works
Self-citationThe Alzheimer's disease Beta-secretase enzyme, BACE1
Cole, S. L., & Vassar, R. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-22 · Cited by 550 · see citing works
Lee, S., Varvel, N. H., Konerth, M. E., Xu, G., Cardona, A. E., Ransohoff, R. M., & Lamb, B. T. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100265 · Cited by 539 · 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
Self-citationContribution of inflammatory processes to Alzheimer's disease: molecular mechanisms
Sastre, M., Klockgether, T., & Heneka, M. T. (2006) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2005.11.014 · Cited by 426 · see citing works
Self-citationThe role of astroglia in neuroprotection
Bélanger, M., & Magistretti, P. J. (2009) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2009.11.3/mbelanger · Cited by 396 · see citing works
Zhao, J., Fu, Y., Yasvoina, M., Shao, P., Hitt, B., O'Connor, T., Logan, S., Maus, E., Citron, M., Berry, R., et al. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4396-06.2007 · Cited by 365 · see citing works
Yamamoto, M., Kiyota, T., Horiba, M., Buescher, J. L., Walsh, S. M., Gendelman, H. E., & Ikezu, T. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.060378 · Cited by 367 · 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
Fang, F., Lue, L.-F., Yan, S., Xu, H., Luddy, J. S., Chen, D., Walker, D. G., Stern, D. M., Yan, S., Schmidt, A. M., et al. (2010) · The FASEB Journal · doi:10.1096/fj.09-139634 · Cited by 335 · see citing works
Delekate, A., Füchtemeier, M., Schumacher, T., Ulbrich, C., Foddis, M., & Petzold, G. C. (2014) · Nature Communications · doi:10.1038/ncomms6422 · Cited by 332 · see citing works
Song, M., Jin, J., Lim, J.-E., Kou, J., Pattanayak, A., Rehman, J. A., Kim, H.-D., Tahara, K., Lalonde, R., & Fukuchi, K.-I. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-92 · Cited by 273 · see citing works
Molecular mechanisms of cognitive dysfunction following traumatic brain injury
Walker, K. R., & Tesco, G. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00029 · Cited by 265 · see citing works
Cholesterol and Alzheimer’s Disease; From Risk Genes to Pathological Effects
Feringa, F. M., & van der Kant, R. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.690372 · Cited by 226 · see citing works
Vallée, A., Lecarpentier, Y., Guillevin, R., & Vallée, J.-N. (2017) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmx073 · Cited by 226 · see citing works
Schiweck, J., Eickholt, B. J., & Murk, K. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00261 · Cited by 223 · see citing works
TREM2 and the neuroimmunology of Alzheimer's disease
Hickman, S. E., & El Khoury, J. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.11.021 · Cited by 221 · see citing works
Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease
Farfara, D., Lifshitz, V., & Frenkel, D. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00314.x · Cited by 216 · see citing works
“It is possible, however, that small soluble aggregates of A trigger local activation of glial cells, as suggested by a recent study of the young thymus cell antigen 1 (Thy1)-APP mice that had not yet developed A deposits [48].”
Chakrabarty, P., Ceballos-Diaz, C., Beccard, A., Janus, C., Dickson, D., Golde, T. E., & Das, P. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903382 · Cited by 206 · see citing works
Yokokura, M., Mori, N., Yagi, S., Yoshikawa, E., Kikuchi, M., Yoshihara, Y., Wakuda, T., Sugihara, G., Takebayashi, K., Suda, S., et al. (2011) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-010-1612-0 · Cited by 174 · see citing works
Chen, Y.-A., Lu, C.-H., Ke, C.-C., Chiu, S.-J., Jeng, F.-S., Chang, C.-W., Yang, B.-H., & Liu, R.-S. (2021) · Biomedicines · doi:10.3390/biomedicines9060594 · Cited by 167 · see citing works
Haure-Mirande, J.-V., Audrain, M., Ehrlich, M. E., & Gandy, S. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00552-w · Cited by 159 · see citing works
Astroglia In Neurological Diseases
Verkhratsky, A., Rodríguez, J. J., & Parpura, V. (2013) · Future Neurology · doi:10.2217/fnl.12.90 · Cited by 140 · see citing works
From cellular senescence to Alzheimer’s disease: The role of telomere shortening
Boccardi, V., Pelini, L., Ercolani, S., Ruggiero, C., & Mecocci, P. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.04.003 · Cited by 121 · see citing works
Welikovitch, L. A., Do Carmo, S., Maglóczky, Z., Malcolm, J. C., Lőke, J., Klein, W. L., Freund, T., & Cuello, A. C. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1914593117 · Cited by 116 · see citing works
Molecular targets of non-steroidal anti-inflammatory drugs in neurodegenerative diseases
Lleo, A., Galea, E., & Sastre, M. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-6516-1 · Cited by 93 · see citing works
Self-citationCalsolaro, V., & Edison, P. (2015) · CNS Drugs · doi:10.1007/s40263-015-0301-8 · Cited by 93 · see citing works
Matousek, S. B., Ghosh, S., Shaftel, S. S., Kyrkanides, S., Olschowka, J. A., & O’Banion, M. K. (2012) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-011-9331-2 · Cited by 86 · see citing works
Mirzaei, N., Tang, S. P., Ashworth, S., Coello, C., Plisson, C., Passchier, J., Selvaraj, V., Tyacke, R. J., Nutt, D. J., & Sastre, M. (2016) · Glia · doi:10.1002/glia.22978 · Cited by 82 · see citing works
Self-citationJin, P., Kim, J.-A., Choi, D.-Y., Lee, Y.-J., Jung, H. S., & Hong, J. T. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-2 · Cited by 59 · see citing works
Increased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer’s disease
Ewers, M., Cheng, X., Zhong, Z., Nural, H. F., Walsh, C., Meindl, T., Teipel, S. J., Buerger, K., He, P., Shen, Y., et al. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-091153 · Cited by 58 · see citing works
Pharmacokinetics of Cromolyn and Ibuprofen in Healthy Elderly Volunteers
Brazier, D., Perry, R., Keane, J., Barrett, K., & Elmaleh, D. R. (2017) · Clinical Drug Investigation · doi:10.1007/s40261-017-0549-5 · Cited by 31 · see citing works
Astrocytic transporters in Alzheimer's disease
Ugbode, C., Hu, Y., Whalley, B., Peers, C., Rattray, M., & Dallas, M. L. (2017) · Biochemical Journal · doi:10.1042/bcj20160505 · Cited by 25 · see citing works
Henao‐Restrepo, J., López‐Murillo, C., Valderrama‐Carmona, P., Orozco‐Santa, N., Gomez, J., Gutiérrez‐Vargas, J., Moraga, R., Toledo, J., Littau, J. L., Härtel, S., et al. (2023) · Brain Pathology · doi:10.1111/bpa.13119 · Cited by 11 · see citing works
- Authors
- Heneka, M. T., Sastre, M., Dumitrescu-Ozimek, L., Dewachter, I., Walter, J., Klockgether, T., & Van Leuven, F.
- Affiliations
- University of Münster (DE)
- University of Bonn (DE)
- KU Leuven (BE)
- Corresponding author
- Heneka, Michael T
- Venue
- Journal of Neuroinflammation
- Published
- 2005-10-07
- Volume
- 2
- Issue
- 1
- Pages
- 22-22
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC1274341
- OpenAlex
- W2124127229
- Cited by
- 309
- References
- 5
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 8 · 2023: 25 · 2022: 14 · 2021: 21 · 2020: 21 · 2019: 18 · 2018: 22 · 2017: 21 · 2016: 12 · 2015: 24 · 2014: 18 · 2013: 19 · 2012: 6
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Document Server@UHasselt (UHasselt) (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (SFB400)
- Fonds Wetenschappelijk Onderzoek
- Vlaamse regering
- 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, glial activation, BACE1, beta-secretase, amyloid plaques, amyloid precursor protein, neuroinflammation, microglia, astrocytes, IL-1β, interleukin-6, MHC class II, macrophage colony-stimulating factor receptor, inducible nitric oxide synthase, peroxynitrite, nitric oxide, amyloid-beta deposition, early neurodegeneration
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
