{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:12:30Z","timestamp":1791270750643,"version":"4.1.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Complement proteins and activation products have been found associated with neuropathology in Alzheimer's disease (AD). Recently, a C5a receptor antagonist was shown to suppress neuropathology in two murine models of AD, Tg2576 and 3xTg. Previously, a genetic deficiency of C1q in the Tg2576 mouse model showed an accumulation of fibrillar plaques similar to the complement sufficient Tg2576, but reactive glia were significantly decreased and neuronal integrity was improved suggesting detrimental consequences for complement activation in AD. The goal of this study was to define the role of the classical complement activation pathway in the progression of pathology in the 3xTg mouse that develops tangles in addition to fibrillar plaques (more closely reflecting human AD pathology) and to assess the influence of complement in a model of AD with a higher level of complement hemolytic activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>3xTg mice deficient in C1q (3xTgQ-\/-) were generated, and both 3xTg and 3xTgQ-\/- were backcrossed to the BUB mouse strain which has higher in vitro hemolytic complement activity. Mice were aged and perfused, and brain sections stained for pathological markers or analyzed for proinflammatory marker expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>3xTgQ-\/- mice showed similar amounts of fibrillar amyloid, reactive glia and hyperphosphorylated tau as the C1q-sufficient 3xTg at the ages analyzed. However, 3xTg and 3xTgQ-\/- on the BUB background developed pathology earlier than on the original 3xTg background, although the presence of C1q had no effect on neuropathological and pro-inflammatory markers. In contrast to that seen in other transgenic models of AD, C1q, C4 and C3 immunoreactivity was undetectable on the plaques of 3xTg in any background, although C3 was associated with reactive astrocytes surrounding the plaques. Importantly, properdin a component of the alternative complement pathway was associated with plaques in all models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In contrast to previously investigated transgenic models of AD, development of neuropathology in 3xTg mice, which progresses much slower than other murine models, may not be influenced by fibrillar amyloid mediated activation of the classical complement pathway, suggesting that the alternative complement pathway activation or a C3-independent cleavage of C5 could account for the detrimental effects in these mice that are prevented by the C5a receptor antagonist. Furthermore, the paucity of complement activation may be a factor in the slower kinetics of progression of pathology in the 3xTg model of this disease.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1742-2094-8-4","type":"journal-article","created":{"date-parts":[[2011,1,19]],"date-time":"2011-01-19T11:14:04Z","timestamp":1295435644000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Contribution of complement activation pathways to neuropathology differs among mouse models of Alzheimer's disease"],"prefix":"10.1186","volume":"8","author":[{"given":"Maria I","family":"Fonseca","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Hui","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisia M","family":"Berci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie E","family":"Benoit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas G","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea J","family":"Tenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,1,15]]},"reference":[{"key":"313_CR1","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1146\/annurev.pharmtox.43.100901.140248","volume":"43","author":"DJ Selkoe","year":"2003","unstructured":"Selkoe DJ, Schenk D: Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol. 2003, 43: 545-584. 10.1146\/annurev.pharmtox.43.100901.140248.","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"313_CR2","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1097\/01.wad.0000165506.60370.94","volume":"19","author":"H Zanjani","year":"2005","unstructured":"Zanjani H, Finch CE, Kemper C, Atkinson J, McKeel D, Morris JC, et al: Complement activation in very early Alzheimer disease. Alzheimer Dis Assoc Disord. 2005, 19: 55-66. 10.1097\/01.wad.0000165506.60370.94.","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"313_CR3","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1006\/exnr.1996.0043","volume":"138","author":"A Afagh","year":"1996","unstructured":"Afagh A, Cummings BJ, Cribbs DH, Cotman CW, Tenner AJ: Localization and cell association of C1q in Alzheimer's disease brain. Exp Neurol. 1996, 138: 22-32. 10.1006\/exnr.1996.0043.","journal-title":"Exp Neurol"},{"key":"313_CR4","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/BF02890024","volume":"56","author":"P Eikelenboom","year":"1989","unstructured":"Eikelenboom P, Hack CE, Rozemuller JM, Stam FC: Complement activation in amyloid plaques in Alzheimer's dementia. Virchows Archiv B Cell Pathol. 1989, 56: 259-262. 10.1007\/BF02890024.","journal-title":"Virchows Archiv B Cell Pathol"},{"key":"313_CR5","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/1742-2094-5-9","volume":"5","author":"DA Loeffler","year":"2008","unstructured":"Loeffler DA, Camp DM, Bennett DA: Plaque complement activation and cognitive loss in Alzheimer's disease. J Neuroinflammation. 2008, 5: 9-10.1186\/1742-2094-5-9.","journal-title":"J Neuroinflammation"},{"key":"313_CR6","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/0197-4580(92)90086-D","volume":"13","author":"SA Johnson","year":"1992","unstructured":"Johnson SA, Lampert-Etchells M, Pasinetti GM, Rozovsky I, Finch C: Complement mRNA in the mammalian brain: Responses to Alzheimer's disease and experimental brain lesioning. Neurobiol Aging. 1992, 13: 641-648. 10.1016\/0197-4580(92)90086-D.","journal-title":"Neurobiol Aging"},{"key":"313_CR7","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S0006-8993(97)00850-0","volume":"769","author":"Y Shen","year":"1997","unstructured":"Shen Y, Li R, McGeer EG, McGeer PL: Neuronal expression of mRNAs for complement proteins of the classical pathway in Alzheimer brain. Brain Res. 1997, 769: 391-395. 10.1016\/S0006-8993(97)00850-0.","journal-title":"Brain Res"},{"key":"313_CR8","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/S0304-3940(01)01842-0","volume":"305","author":"Y Shen","year":"2001","unstructured":"Shen Y, Lue L, Yang L, Roher A, Kuo Y, Strohmeyer R, et al: Complement activation by neurofibrillary tangles in Alzheimer's disease. Neurosci Lett. 2001, 305: 165-168. 10.1016\/S0304-3940(01)01842-0.","journal-title":"Neurosci Lett"},{"key":"313_CR9","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/S0197-4580(97)00042-0","volume":"18","author":"S Webster","year":"1997","unstructured":"Webster S, Lue LF, Brachova L, Tenner AJ, McGeer PL, Terai K, et al: Molecular and cellular characterization of the membrane attack complex, C5b-9, in Alzheimer's disease. Neurobiol Aging. 1997, 18: 415-421. 10.1016\/S0197-4580(97)00042-0.","journal-title":"Neurobiol Aging"},{"key":"313_CR10","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/S0197-4580(00)00124-X","volume":"21","author":"H Akiyama","year":"2000","unstructured":"Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, et al: Inflammation and Alzheimer's disease. Neurobiol Aging. 2000, 21: 383-421. 10.1016\/S0197-4580(00)00124-X.","journal-title":"Neurobiol Aging"},{"key":"313_CR11","doi-asserted-by":"publisher","first-page":"10016","DOI":"10.1073\/pnas.89.21.10016","volume":"89","author":"J Rogers","year":"1992","unstructured":"Rogers J, Cooper NR, Webster S, Schultz J, McGeer PL, Styren SD, et al: Complement activation by beta-amyloid in Alzheimer disease. Proc Natl Acad Sci. 1992, 89: 10016-10020. 10.1073\/pnas.89.21.10016.","journal-title":"Proc Natl Acad Sci"},{"key":"313_CR12","doi-asserted-by":"crossref","first-page":"5050","DOI":"10.4049\/jimmunol.152.10.5050","volume":"152","author":"H Jiang","year":"1994","unstructured":"Jiang H, Burdick D, Glabe CG, Cotman CW, Tenner AJ: b-amyloid activates complement by binding to a specific region of the collagen-like domain of the C1q A chain. J Immunol. 1994, 152: 5050-5059.","journal-title":"J Immunol"},{"key":"313_CR13","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1084\/jem.188.3.431","volume":"188","author":"BM Bradt","year":"1998","unstructured":"Bradt BM, Kolb WP, Cooper NR: Complement-dependent proinflammatory properties of the Alzheimer's disease beta-peptide. J Exp Med. 1998, 188: 431-438. 10.1084\/jem.188.3.431.","journal-title":"J Exp Med"},{"key":"313_CR14","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1002\/jnr.490270106","volume":"27","author":"J Yao","year":"1990","unstructured":"Yao J, Harvath L, Gilbert DL, Colton CA: Chemotaxis by a CNS macrophage, the microglia. J Neurosci Res. 1990, 27: 36-42. 10.1002\/jnr.490270106.","journal-title":"J Neurosci Res"},{"key":"313_CR15","first-page":"119","volume-title":"Inflammatory Events in Neurodegeneration","author":"AJ Tenner","year":"2001","unstructured":"Tenner AJ, Webster SD: Complement-mediated injury and inflammation in the pathogenesis of Alzheimer's Disease. Inflammatory Events in Neurodegeneration. Edited by: Bondy SC, Campbell A Scottsdale, AZ. 2001, Prominent Press, 119-138."},{"key":"313_CR16","doi-asserted-by":"publisher","first-page":"6457","DOI":"10.1523\/JNEUROSCI.0901-04.2004","volume":"24","author":"MI Fonseca","year":"2004","unstructured":"Fonseca MI, Zhou J, Botto M, Tenner AJ: Absence of C1q leads to less neuropathology in transgenic mouse models of Alzheimer's disease. J Neurosci. 2004, 24: 6457-6465. 10.1523\/JNEUROSCI.0901-04.2004.","journal-title":"J Neurosci"},{"key":"313_CR17","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.4049\/jimmunol.0901005","volume":"183","author":"MI Fonseca","year":"2009","unstructured":"Fonseca MI, Ager RR, Chu SH, Yazan O, Sanderson SD, LaFerla FM, et al: Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's disease. J Immunol. 2009, 183: 1375-1383. 10.4049\/jimmunol.0901005.","journal-title":"J Immunol"},{"key":"313_CR18","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/S0896-6273(03)00434-3","volume":"39","author":"S Oddo","year":"2003","unstructured":"Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, et al: Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron. 2003, 39: 409-421. 10.1016\/S0896-6273(03)00434-3.","journal-title":"Neuron"},{"key":"313_CR19","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/0022-1759(89)90088-4","volume":"125","author":"GL Ong","year":"1989","unstructured":"Ong GL, Mattes MJ: Mouse strains with typical mammalian levels of complement activity. J Immunol Methods. 1989, 125: 147-158. 10.1016\/0022-1759(89)90088-4.","journal-title":"J Immunol Methods"},{"key":"313_CR20","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/0022-1759(92)90210-K","volume":"154","author":"GL Ong","year":"1992","unstructured":"Ong GL, Baker AE, Mattes MJ: Analysis of high complement levels in Mus hortulanus and BUB mice. J Immunol Methods. 1992, 154: 37-45. 10.1016\/0022-1759(92)90210-K.","journal-title":"J Immunol Methods"},{"key":"313_CR21","doi-asserted-by":"publisher","first-page":"13876","DOI":"10.1523\/JNEUROSCI.2823-08.2008","volume":"28","author":"MD Galvan","year":"2008","unstructured":"Galvan MD, Luchetti S, Burgos AM, Nguyen HX, Hooshmand MJ, Hamers FP, et al: Deficiency in complement C1q improves histological and functional locomotor outcome after spinal cord injury. J Neurosci. 2008, 28: 13876-13888. 10.1523\/JNEUROSCI.2823-08.2008.","journal-title":"J Neurosci"},{"key":"313_CR22","doi-asserted-by":"publisher","first-page":"1722","DOI":"10.1016\/j.molimm.2005.10.004","volume":"43","author":"I Osmers","year":"2006","unstructured":"Osmers I, Szalai AJ, Tenner AJ, Barnum SR: Complement in BuB\/BnJ mice revisited: serum C3 levels and complement opsonic activity are not elevated. Mol Immunol. 2006, 43: 1722-1725. 10.1016\/j.molimm.2005.10.004.","journal-title":"Mol Immunol"},{"key":"313_CR23","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/ng0598-56","volume":"19","author":"M Botto","year":"1998","unstructured":"Botto M, Dell'agnola C, Bygrave AE, Thompson EM, Cook HT, Petry F, et al: Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet. 1998, 19: 56-59. 10.1038\/ng0598-56.","journal-title":"Nat Genet"},{"key":"313_CR24","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.brainres.2008.03.079","volume":"1216","author":"C Hirata-Fukae","year":"2008","unstructured":"Hirata-Fukae C, Li HF, Hoe HS, Gray AJ, Minami SS, Hamada K, et al: Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. Brain Res. 2008, 1216: 92-103. 10.1016\/j.brainres.2008.03.079.","journal-title":"Brain Res"},{"key":"313_CR25","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1126\/science.274.5284.99","volume":"274","author":"KK Hsiao","year":"1996","unstructured":"Hsiao KK, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, et al: Correlative memory deficits, Ab elevations, and amyloid plaques in transgenic mice. Science. 1996, 274: 99-102. 10.1126\/science.274.5284.99.","journal-title":"Science"},{"key":"313_CR26","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1038\/nm1123","volume":"10","author":"IH Cheng","year":"2004","unstructured":"Cheng IH, Palop JJ, Esposito LA, Bien-Ly N, Yan F, Mucke L: Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation. Nat Med. 2004, 10: 1190-1192. 10.1038\/nm1123.","journal-title":"Nat Med"},{"key":"313_CR27","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1126\/science.285.5427.595","volume":"285","author":"J Huang","year":"1999","unstructured":"Huang J, Kim LJ, Mealey R, Marsh HC, Zhang Y, Tenner AJ, et al: Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein. Science. 1999, 285: 595-599. 10.1126\/science.285.5427.595.","journal-title":"Science"},{"key":"313_CR28","doi-asserted-by":"publisher","first-page":"3545","DOI":"10.1172\/JCI41782","volume":"120","author":"Y Kimura","year":"2010","unstructured":"Kimura Y, Zhou L, Miwa T, Song WC: Genetic and therapeutic targeting of properdin in mice prevents complement-mediated tissue injury. J Clin Invest. 2010, 120: 3545-3554. 10.1172\/JCI41782.","journal-title":"J Clin Invest"},{"key":"313_CR29","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1006\/exnr.1999.7058","volume":"157","author":"MI Fonseca","year":"1999","unstructured":"Fonseca MI, Head E, Velazquez P, Cotman CW, Tenner AJ: The presence of isoaspartic acid in beta-amyloid plaques indicates plaque age. Exp Neurol. 1999, 157: 277-288. 10.1006\/exnr.1999.7058.","journal-title":"Exp Neurol"},{"key":"313_CR30","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","volume":"3","author":"TD Schmittgen","year":"2008","unstructured":"Schmittgen TD, Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008, 3: 1101-1108. 10.1038\/nprot.2008.73.","journal-title":"Nat Protoc"},{"key":"313_CR31","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1016\/S0002-9440(10)64085-0","volume":"158","author":"Y Matsuoka","year":"2001","unstructured":"Matsuoka Y, Picciano M, Malester B, LaFrancois J, Zehr C, Daeschner JM, et al: Inflammatory responses to amyloidosis in a transgenic mouse model of Alzheimer's disease. Am J Pathol. 2001, 158: 1345-1354.","journal-title":"Am J Pathol"},{"key":"313_CR32","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/1742-2094-6-35","volume":"6","author":"J Reichwald","year":"2009","unstructured":"Reichwald J, Danner S, Wiederhold KH, Staufenbiel M: Expression of complement system components during aging and amyloid deposition in APP transgenic mice. J Neuroinflammation. 2009, 6: 35-10.1186\/1742-2094-6-35.","journal-title":"J Neuroinflammation"},{"key":"313_CR33","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.1111\/j.1471-4159.2008.05558.x","volume":"106","author":"J Zhou","year":"2008","unstructured":"Zhou J, Fonseca MI, Pisalyaput K, Tenner AJ: Complement C3 and C4 expression in C1q sufficient and deficient mouse models of Alzheimer's disease. J Neurochem. 2008, 106: 2080-2092. 10.1111\/j.1471-4159.2008.05558.x.","journal-title":"J Neurochem"},{"key":"313_CR34","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1016\/j.molimm.2003.10.019","volume":"40","author":"D Mastellos","year":"2004","unstructured":"Mastellos D, Prechl J, Laszlo G, Papp K, Olah E, Argyropoulos E, et al: Novel monoclonal antibodies against mouse C3 interfering with complement activation: description of fine specificity and applications to various immunoassays. Mol Immunol. 2004, 40: 1213-1221. 10.1016\/j.molimm.2003.10.019.","journal-title":"Mol Immunol"},{"key":"313_CR35","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/nm1419","volume":"12","author":"M Huber-Lang","year":"2006","unstructured":"Huber-Lang M, Sarma JV, Zetoune FS, Rittirsch D, Neff TA, McGuire SR, et al: Generation of C5a in the absence of C3: a new complement activation pathway. Nat Med. 2006, 12: 682-687. 10.1038\/nm1419.","journal-title":"Nat Med"},{"key":"313_CR36","doi-asserted-by":"publisher","first-page":"158","DOI":"10.2174\/138945008783502458","volume":"9","author":"DE Hourcade","year":"2008","unstructured":"Hourcade DE: Properdin and complement activation: a fresh perspective. Curr Drug Targets. 2008, 9: 158-164. 10.2174\/138945008783502458.","journal-title":"Curr Drug Targets"},{"key":"313_CR37","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s12017-009-8085-y","volume":"12","author":"TM Woodruff","year":"2010","unstructured":"Woodruff TM, Ager RR, Tenner AJ, Noakes PG, Taylor SM: The role of the complement system and the activation fragment C5a in the central nervous system. Neuromolecular Med. 2010, 12: 179-192. 10.1007\/s12017-009-8085-y.","journal-title":"Neuromolecular Med"},{"key":"313_CR38","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1016\/j.neurobiolaging.2007.02.017","volume":"29","author":"D Ryman","year":"2008","unstructured":"Ryman D, Gao Y, Lamb BT: Genetic loci modulating amyloid-beta levels in a mouse model of Alzheimer's disease. Neurobiol Aging. 2008, 29: 1190-1198. 10.1016\/j.neurobiolaging.2007.02.017.","journal-title":"Neurobiol Aging"},{"key":"313_CR39","doi-asserted-by":"publisher","first-page":"5088","DOI":"10.1016\/j.bmcl.2006.07.036","volume":"16","author":"K Schnatbaum","year":"2006","unstructured":"Schnatbaum K, Locardi E, Scharn D, Richter U, Hawlisch H, Knolle J, et al: Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. Bioorg Med Chem Lett. 2006, 16: 5088-5092. 10.1016\/j.bmcl.2006.07.036.","journal-title":"Bioorg Med Chem Lett"},{"key":"313_CR40","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1111\/j.1471-4159.2007.05012.x","volume":"104","author":"K Pisalyaput","year":"2008","unstructured":"Pisalyaput K, Tenner AJ: Complement component C1q inhibits beta-amyloid- and serum amyloid P-induced neurotoxicity via caspase- and calpain-independent mechanisms. J Neurochem. 2008, 104: 696-707.","journal-title":"J Neurochem"},{"key":"313_CR41","doi-asserted-by":"publisher","first-page":"6333","DOI":"10.1523\/JNEUROSCI.0829-08.2008","volume":"28","author":"M Maier","year":"2008","unstructured":"Maier M, Peng Y, Jiang L, Seabrook TJ, Carroll MC, Lemere CA: Complement C3 deficiency leads to accelerated amyloid beta plaque deposition and neurodegeneration and modulation of the microglia\/macrophage phenotype in amyloid precursor protein transgenic mice. J Neurosci. 2008, 28: 6333-6341. 10.1523\/JNEUROSCI.0829-08.2008.","journal-title":"J Neurosci"},{"key":"313_CR42","first-page":"1005","volume":"12","author":"T Wyss-Coray","year":"2006","unstructured":"Wyss-Coray T: Inflammation in Alzheimer disease: driving force, bystander or beneficial response?. Nat Med. 2006, 12: 1005-1015.","journal-title":"Nat Med"},{"key":"313_CR43","doi-asserted-by":"publisher","first-page":"10837","DOI":"10.1073\/pnas.162350199","volume":"99","author":"T Wyss-Coray","year":"2002","unstructured":"Wyss-Coray T, Yan F, Lin AH, Lambris JD, Alexander JJ, Quigg RJ, et al: Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer's mice. Proc Natl Acad Sci USA. 2002, 99: 10837-10842. 10.1073\/pnas.162350199.","journal-title":"Proc Natl Acad Sci USA"},{"key":"313_CR44","doi-asserted-by":"publisher","first-page":"5333","DOI":"10.4049\/jimmunol.0903382","volume":"184","author":"P Chakrabarty","year":"2010","unstructured":"Chakrabarty P, Ceballos-Diaz C, Beccard A, Janus C, Dickson D, Golde TE, et al: IFN-gamma promotes complement expression and attenuates amyloid plaque deposition in amyloid beta precursor protein transgenic mice. J Immunol. 2010, 184: 5333-5343. 10.4049\/jimmunol.0903382.","journal-title":"J Immunol"},{"key":"313_CR45","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1742-2094-4-22","volume":"4","author":"R Fan","year":"2007","unstructured":"Fan R, DeFilippis K, Van Nostrand WE: Induction of complement proteins in a mouse model for cerebral microvascular A beta deposition. J Neuroinflammation. 2007, 4: 22-10.1186\/1742-2094-4-22.","journal-title":"J Neuroinflammation"},{"key":"313_CR46","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.it.2008.11.003","volume":"30","author":"AP Sjoberg","year":"2009","unstructured":"Sjoberg AP, Trouw LA, Blom AM: Complement activation and inhibition: a delicate balance. Trends Immunol. 2009, 30: 83-90. 10.1016\/j.it.2008.11.003.","journal-title":"Trends Immunol"},{"key":"313_CR47","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1006\/exnr.1999.7199","volume":"160","author":"R Veerhuis","year":"1999","unstructured":"Veerhuis R, Janssen I, De Groot CJ, Van Muiswinkel FL, Hack CE, Eikelenboom P: Cytokines associated with amyloid plaques in Alzheimer's disease brain stimulate human glial and neuronal cell cultures to secrete early complement proteins, but not C1-inhibitor. Exp Neurol. 1999, 160: 289-299. 10.1006\/exnr.1999.7199.","journal-title":"Exp Neurol"},{"key":"313_CR48","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1006\/exnr.1999.7170","volume":"159","author":"SK Singhrao","year":"1999","unstructured":"Singhrao SK, Neal JW, Morgan BP, Gasque P: Increased complement biosynthesis by microglia and complement activation on neurons in Huntington's disease. Exp Neurol. 1999, 159: 362-376. 10.1006\/exnr.1999.7170.","journal-title":"Exp Neurol"},{"key":"313_CR49","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.expneurol.2004.03.016","volume":"188","author":"C Schwab","year":"2004","unstructured":"Schwab C, Hosokawa M, McGeer PL: Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease. Exp Neurol. 2004, 188: 52-64. 10.1016\/j.expneurol.2004.03.016.","journal-title":"Exp Neurol"},{"key":"313_CR50","doi-asserted-by":"publisher","first-page":"5174","DOI":"10.1128\/JVI.79.8.5174-5184.2005","volume":"79","author":"C Cunningham","year":"2005","unstructured":"Cunningham C, Wilcockson DC, Boche D, Perry VH: Comparison of inflammatory and acute-phase responses in the brain and peripheral organs of the ME7 model of prion disease. J Virol. 2005, 79: 5174-5184. 10.1128\/JVI.79.8.5174-5184.2005.","journal-title":"J Virol"},{"key":"313_CR51","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/S0002-9440(10)64753-0","volume":"156","author":"SE Stoltzner","year":"2000","unstructured":"Stoltzner SE, Grenfell TJ, Mori C, Wisniewski KE, Wisniewski TM, Selkoe DJ, et al: Temporal accrual of complement proteins in amyloid plaques in Down's syndrome with Alzheimer's disease. Am J Pathol. 2000, 156: 489-499.","journal-title":"Am J Pathol"},{"key":"313_CR52","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.nbd.2003.09.004","volume":"15","author":"MI Fonseca","year":"2004","unstructured":"Fonseca MI, Kawas CH, Troncoso JC, Tenner AJ: Neuronal localization of C1q in preclinical Alzheimer's disease. Neurobiol Dis. 2004, 15: 40-46. 10.1016\/j.nbd.2003.09.004.","journal-title":"Neurobiol Dis"},{"key":"313_CR53","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/S0169-328X(00)00149-2","volume":"81","author":"R Strohmeyer","year":"2000","unstructured":"Strohmeyer R, Shen Y, Rogers J: Detection of complement alternative pathway mRNA and proteins in the Alzheimer's disease brain. Brain Res Mol Brain Res. 2000, 81: 7-18. 10.1016\/S0169-328X(00)00149-2.","journal-title":"Brain Res Mol Brain Res"},{"key":"313_CR54","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/S0166-2236(98)01390-3","volume":"22","author":"S Nataf","year":"1999","unstructured":"Nataf S, Stahel PF, Davoust N, Barnum SR: Complement anaphylatoxin receptors on neurons: new tricks for old receptors?. Trends Neurosci. 1999, 22: 397-402. 10.1016\/S0166-2236(98)01390-3.","journal-title":"Trends Neurosci"},{"key":"313_CR55","first-page":"83","volume":"24","author":"DR Howlett","year":"2009","unstructured":"Howlett DR, Richardson JC: The pathology of APP transgenic mice: a model of Alzheimer's disease or simply overexpression of APP?. Histol Histopathol. 2009, 24: 83-100.","journal-title":"Histol Histopathol"},{"key":"313_CR56","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s00401-007-0312-8","volume":"115","author":"C Duyckaerts","year":"2008","unstructured":"Duyckaerts C, Potier MC, Delatour B: Alzheimer disease models and human neuropathology: similarities and differences. Acta Neuropathol. 2008, 115: 5-38. 10.1007\/s00401-007-0312-8.","journal-title":"Acta Neuropathol"},{"key":"313_CR57","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1111\/j.1471-4159.2008.05668.x","volume":"107","author":"JJ Alexander","year":"2008","unstructured":"Alexander JJ, Anderson AJ, Barnum SR, Stevens B, Tenner AJ: The complement cascade: Yin-Yang in neuroinflammation--neuro-protection and -degeneration. J Neurochem. 2008, 107: 1169-1187. 10.1111\/j.1471-4159.2008.05668.x.","journal-title":"J Neurochem"},{"key":"313_CR58","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.neuron.2010.04.031","volume":"66","author":"KH Ashe","year":"2010","unstructured":"Ashe KH, Zahs KR: Probing the Biology of Alzheimer's Disease in Mice. Neuron. 2010, 66: 631-645. 10.1016\/j.neuron.2010.04.031.","journal-title":"Neuron"},{"key":"313_CR59","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.neuron.2009.08.039","volume":"64","author":"KM Lucin","year":"2009","unstructured":"Lucin KM, Wyss-Coray T: Immune activation in brain aging and neurodegeneration: too much or too little?. Neuron. 2009, 64: 110-122. 10.1016\/j.neuron.2009.08.039.","journal-title":"Neuron"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1742-2094-8-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T08:01:50Z","timestamp":1712131310000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/1742-2094-8-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1,15]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,12]]}},"alternative-id":["313"],"URL":"https:\/\/doi.org\/10.1186\/1742-2094-8-4","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1,15]]},"assertion":[{"value":"26 August 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2011","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2011","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"4"}}