Pathogenic mechanisms of Alzheimer's disease analyzed in the APP23 transgenic mouse model.
APP23 transgenic mice overexpress human APP with the Swedish double mutation. The mice start to develop amyloid plaque pathology at about six months of age, followed somewhat later by vascular amyloid deposits. Plaques are mostly of the compact type and increase exponentially during aging. Female mice show a slightly more rapid A beta plaque deposition than do male animals. Associated with the amyloid are inflammatory reactions, neuritic and synaptic degeneration as well as tau hyperphosphorylation. Older mice have a reduced cholinergic fiber length and a reduced neuron number in the hippocampal CA1 region. Crossbreeding with transgenic mice expressing human presenilin 1 carrying Alzheimer's disease-linked mutations lead to an enhancement of the pathology. The APP23 line is a suitable model to analyze the contribution of APP, A beta, and amyloid to the pathogenesis of Alzheimer's disease.
Sturchler-Pierrat
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Nervous System Research, Novartis Pharma Inc., CH-4002 Basel, Switzerland.
Staufenbiel
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D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000032:analysis; D000818:Animals; D001921:Brain / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009412:Nerve Fibers / Q000473:pathology; D009474:Neurons / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins