Increased fibrillar beta-amyloid in response to human clq injections into hippocampus and cortex of APP+PS1 transgenic mice.
Human C1q when injected directly into hippocampus and cortex of doubly transgenic APP+PS1 mice results in the increase of Congo red-positive fibrillar deposits. Although there was no significant change in overall area stained for Abeta total, qualitatively it appeared that there was less diffuse Abeta in C1q-treated mice versus vehicle. There was no apparent change in astroglial or microglial activation caused by injection of C1q with respect to vehicle injections. These effects of C1q were only found in 50% BUB/BnJ mice, a strain with higher serum complement activity than other mouse lines. These in vivo data were consistent with the effects of C1q to increase fibrillogenesis of Abeta in vitro. In conclusion, complement protein C1q, believed to be involved in the pathogenesis of Alzheimer's disease in humans, can cause increased fibrillogenesis in the APP+PS1 mouse model of amyloid deposition.
Boyett
Kristal W
KW
Alzheimer's Research Laboratory, Department of Pharmacology and Therapeutics, Tampa, Florida 33612, USA.
DiCarlo
Giovanni
G
Jantzen
Paul T
PT
Jackson
Jennifer
J
O'Leary
Charlotte
C
Wilcock
Donna
D
Morgan
Dave
D
Gordon
Marcia N
MN
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000502:physiology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D015922:Complement C1q / Q000008:administration & dosage*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D015922:Complement C1q