Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease - PubMed (original) (raw)
Comparative Study
Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease
Claudia Schwab et al. Exp Neurol. 2004 Jul.
Abstract
We compared lesions in elderly transgenic (tg) mice carrying the Swedish double mutation KM670/671NL with lesions in Alzheimer disease (AD) by histochemical and immunohistochemical techniques. Highly similar staining for beta-amyloid protein (Abeta) was observed in AD and the mouse models. The abundant amyloid deposits in tg mice were in a consolidated state as revealed by strong Congo red birefringence. In both tg mice and AD, amyloid deposits were ApoE-positive and were surrounded by activated astrocytes. However, Bielschowsky silver staining and immunostaining with tau antibodies revealed no neurofibrillary tangles (NFTs) in the mice as opposed to abundant NFTs in AD. The microglial pattern was also distinctly different. Tg mice had only weakly activated microglia, which expressed low levels of the complement receptor CD11b. They were gathered around the periphery of the deposits. In contrast, AD lesions had strongly activated microglia, which expressed high levels of CD11b. They were associated with the plaque core. Immunostaining for complement proteins was weak in tg mice but very strong in AD deposits. We conclude that the weak inflammatory response and absence of NFTs indicate that tg mice are only a limited model of AD. Therapeutic strategies for the treatment of AD based on tg mouse models that overexpress Abeta may be limited in their application.
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