QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 21, 2004, 24(29):6457-6465; doi:10.1523/JNEUROSCI.0901-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (39) Citing Articles via Google Scholar Google Scholar Articles by Fonseca, M. I. Articles by Tenner, A. J. Search for Related Content PubMed PubMed Citation Articles by Fonseca, M. I. Articles by Tenner, A. J.

 Previous Article  |  Next Article 

Neurobiology of Disease
Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease

Maria Isabel Fonseca,¹ Jun Zhou,¹ Marina Botto,² and Andrea J. Tenner¹

¹Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, and ²Rheumatology Section, Imperial College, London, United Kingdom

C1q, the recognition component of the classical complement activation pathway, is a multifunctional protein known to be expressed in brain of Alzheimer's disease (AD) patients. To experimentally address the role of C1q in AD, a mouse model lacking C1q (APPQ-/-) was generated by crossing Tg2576 animals (APP) with C1q-deficient mice. The pathology of APPQ-/- was compared with that of APP mice and B6SJL controls at 3-16 months of age by immunohistochemistry and Western blot analysis. At younger ages (3-6 months), when no plaque pathology was present, no significant differences were seen in any of the neuronal or glial markers tested. At older ages (9-16 months), the APP and APPQ-/- mice developed comparable total amyloid and fibrillar -amyloid in frontal cortex and hippocampus; however, the level of activated glia surrounding the plaques was significantly lower in the APPQ-/- mice at 12 and 16 months. In addition, although Tg2576 mice showed a progressive decrease in synaptophysin and MAP2 in the CA3 area of hippocampus compared with control B6SJL at 9, 12, and 16 months, the APPQ-/- mice had significantly less of a decrease in these markers at 12 and 16 months. In a second murine model for AD containing transgenes for both APP and mutant presenilin 1 (APP/PS1), a similar reduction of pathology was seen in the APPPS1Q-/- mice. These data suggest that at ages when the fibrillar plaque pathology is present, C1q exerts a detrimental effect on neuronal integrity, most likely through the activation of the classical complement cascade and the enhancement of inflammation.

Key words: complement; C1q; inflammation; Alzheimer's disease; transgenic models; neuropathology

---

Received Nov 6, 2003; revised June 8, 2004; accepted June 9, 2004.

This article has been cited by other articles:

				M. I. Fonseca, R. R. Ager, S.-H. Chu, O. Yazan, S. D. Sanderson, F. M. LaFerla, S. M. Taylor, T. M. Woodruff, and A. J. Tenner Treatment with a C5aR Antagonist Decreases Pathology and Enhances Behavioral Performance in Murine Models of Alzheimer's Disease J. Immunol., July 15, 2009; 183(2): 1375 - 1383. [Abstract] [Full Text] [PDF]

				M. D. Galvan, S. Luchetti, A. M. Burgos, H. X. Nguyen, M. J. Hooshmand, F. P. T. Hamers, and A. J. Anderson Deficiency in Complement C1q Improves Histological and Functional Locomotor Outcome after Spinal Cord Injury J. Neurosci., December 17, 2008; 28(51): 13876 - 13888. [Abstract] [Full Text] [PDF]

				Y. Ding, A. Qiao, Z. Wang, J. S. Goodwin, E.-S. Lee, M. L. Block, M. Allsbrook, M. P. McDonald, and G.-H. Fan Retinoic Acid Attenuates {beta}-Amyloid Deposition and Rescues Memory Deficits in an Alzheimer's Disease Transgenic Mouse Model J. Neurosci., November 5, 2008; 28(45): 11622 - 11634. [Abstract] [Full Text] [PDF]

				E. Herczenik and M. F. B. G. Gebbink Molecular and cellular aspects of protein misfolding and disease FASEB J, July 1, 2008; 22(7): 2115 - 2133. [Abstract] [Full Text] [PDF]

				M. Maier, Y. Peng, L. Jiang, T. J. Seabrook, M. C. Carroll, and C. A. Lemere 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., June 18, 2008; 28(25): 6333 - 6341. [Abstract] [Full Text] [PDF]

				J. Schmidt, K. Barthel, A. Wrede, M. Salajegheh, M. Bahr, and M. C. Dalakas Interrelation of inflammation and APP in sIBM: IL-1{beta} induces accumulation of {beta}-amyloid in skeletal muscle Brain, May 1, 2008; 131(5): 1228 - 1240. [Abstract] [Full Text] [PDF]

				C. S. Lobsiger, S. Boillee, and D. W. Cleveland Inaugural Article: Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons PNAS, May 1, 2007; 104(18): 7319 - 7326. [Abstract] [Full Text] [PDF]

				M. R. D'Andrea Evidence that immunoglobulin-positive neurons in Alzheimer's disease are dying via the classical antibody-dependent complement pathway American Journal of Alzheimer's Disease and Other Dementias, May 1, 2005; 20(3): 144 - 150. [Abstract] [PDF]

				M. Yamamoto, M. Horiba, J. L. Buescher, D. Huang, H. E. Gendelman, R. M. Ransohoff, and T. Ikezu Overexpression of Monocyte Chemotactic Protein-1/CCL2 in {beta}-Amyloid Precursor Protein Transgenic Mice Show Accelerated Diffuse {beta}-Amyloid Deposition Am. J. Pathol., May 1, 2005; 166(5): 1475 - 1485. [Abstract] [Full Text] [PDF]

				Papers of Note Sci. Aging Knowl. Environ., July 28, 2004; 2004(30): nw29 - nw29. [Full Text]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help