The pathology of APP transgenic mice: a model of Alzheimer’s disease or simply overexpression of APP?

D.R. Howlett and J.C. Richardson

Neurology CEDD, GlaxoSmithKline, Harlow, Essex, UK.

Offprint requests to: D.R. Howlett, Neurology CEDD, GlaxoSmithKline, Harlow, Essex, CM19 5AD, UK. e-mail: david.r.howlett@gsk.com


Summary. Alzheimer’s disease (AD) is characterized by a number of pathological features, notably extracellular senile plaques composed of the beta-amyloid protein (Aß) and neurofibrillary tangles (NFT’s), which are intracellular inclusions of hyperphosphorylated tau protein. In their attempts to generate a model of AD, many laboratories have produced transgenic mice that overexpress the amyloid precursor protein (APP), in particular, mutant APP which is associated with familial forms of AD in man. Histopathological assessment shows that APP transgenic mice demonstrate an accumulation of Aß in plaques from an early age; these plaques are invariably surrounded by activated inflammatory cells such as astrocytes and microglia, as is common in AD brain. Also, commonly associated with the plaques is hyperphosphorylated tau, although this does not take on the NFT phenotype observed in AD. Atrophy and neurodegenerative pathology are other common features of AD; some neuronal loss is evident in close proximity to plaques in APP transgenic mice although this is not extensive. Consequently, it is evident that APP transgenic mice exhibit, to some degree, many of the pathological features of AD. Histol Histopathol 24, 83-100 (2009)

Key words: Alzheimer’s disease, Neurodegenerative pathology, Amyloid plaques

DOI: 10.14670/HH-24.83