Expression of complement system components during aging and amyloid deposition in APP transgenic mice

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• The complement system's role in Alzheimer's disease (AD) is suggested by activated components at amyloid plaques.
• Previous studies in APP transgenic mice showed only early complement cascade activation.
• Understanding aging and amyloid's impact on complement activation is crucial.

Purpose of the Study:

• To characterize the expression of major mouse complement components.
• To investigate age- and amyloid-induced changes in complement expression.

Main Methods:

• Real-time PCR for mRNA quantification in APP23 and C57BL/6 mice.
• Western blotting for complement C1q and C3 protein levels.
• Histology to assess amyloid plaque association and complement activation.

Main Results:

• High mRNA for C1q and inhibitory components; low for activating components (e.g., C3).
• Age-dependent increase in C1q, C3, C4, C5, and factor B mRNA in controls.
• Amyloid deposition in APP23 mice further elevated C1q and C3 mRNA and protein levels, with complement recruitment up to C3 convertase.

Conclusions:

• Early complement components increase with age in mice; amyloid deposition has a smaller effect.
• Low expression of C3 and C5, and lack of downstream component upregulation, contrasts with human AD.
• These differences likely explain incomplete complement activation in APP transgenic mouse models.