For years, rats have been the creature of choice for students of learning and behavior, as well as in pharmacology. Yet in the AD field, lab cages house mostly mice. Transgenic, knockout, knock-in, conditional—the increasing ease of genetic tinkering has engendered development of dozens of custom strains to study aspects of AD pathology.
But to make a better model for memory and behavioral testing, Eirikur Benedikz of the Karolinska Institute in Stockholm, Sweden, and colleagues turned to rats. In the May 8 Biochemical and Biophysical Research Communications, the researchers describe their transgenic Sprague-Dawley rats that express human amyloid precursor protein with the Swedish mutation. The highest levels of human APP expression occurs in the cortex, hippocampus, and cerebellum. From 15 months on, the rats show increased extracellular amyloid-β peptides and tau phosphorylation. The Aβ deposits mostly in blood vessels, but rare diffuse plaques occurred in cortex. The investigators saw no neurofibrillary tangles.
The finding of extracellular Aβ is significant. A previous transgenic rat incorporating mutant forms of human APP and presenilin 1 showed intracellular Aβ deposition but no extracellular amyloid (Echeverria et al., 2004). Benedikz and colleagues write, “We believe that these rats represent a unique model of early AD and that crossing these animals with mutant PS1 transgenic rats will result in accelerated plaque formation similar to that seen in transgenic mice.”—Pat McCaffrey
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- Folkesson R, Malkiewicz K, Kloskowska E, Nilsson T, Popova E, Bogdanovic N, Ganten U, Ganten D, Bader M, Winblad B, Benedikz E. A transgenic rat expressing human APP with the Swedish Alzheimer's disease mutation. Biochem Biophys Res Commun. 2007 Jul 6;358(3):777-82. PubMed.