Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease
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Machine scores (provisional)
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- Teacher spread
- 0.268 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
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 beta-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.
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The record
- Venue
- Journal of Neuroscience
- Topic
- Alzheimer's disease research and treatments
- Field
- Medicine
- Canadian institutions
- —
- Funders
- National Institute on AgingNational Institutes of HealthNational Institute of Neurological Disorders and StrokeYork University
- Keywords
- PresenilinGenetically modified mouseSynaptophysinHippocampusNeuropathologyHippocampal formationPathologyAmyloid precursor proteinImmunohistochemistryTransgeneWestern blotComplement systemAlzheimer's diseaseNeuroscienceBiologyMedicineDiseaseImmunologyAntibody
- Has abstract in OpenAlex
- yes