Normal cognition in transgenic BRI2-Aβ mice

Background: Recent research in Alzheimer's disease (AD) field has been focused on the potential role of the amyloid-beta protein that is derived from the transmembrane amyloid precursor protein (APP) in directly mediating cognitive impairment in AD. Transgenic mouse models overexpressing APP develop robust AD-like amyloid pathology in the brain and show various levels of cognitive decline. In the present study, we examined the cognition of the BRI2-A beta transgenic mouse model in which secreted extracellular A beta 1-40, A beta 1-42 or both A beta 1-40/A beta 1-42 peptides are generated from the BRI-A beta fusion proteins encoded by the transgenes. BRI2-A beta mice produce high levels of A beta peptides and BRI2-A beta 1-42 mice develop amyloid pathology that is similar to the pathology observed in mutant human APP transgenic models. Results: Using established behavioral tests that reveal deficits in APP transgenic models, BRI2-A beta 1-42 mice showed completely intact cognitive performance at ages both pre and post amyloid plaque formation. BRI2-A beta mice producing A beta 1-40 or both peptides were also cognitively intact. Conclusions: These data indicate that high levels of A beta 1-40 or A beta 1-42, or both produced in the absence of APP overexpression do not reproduce memory deficits observed in APP transgenic mouse models. This outcome is supportive of recent data suggesting that APP processing derivatives or the overexpression of full length APP may contribute to cognitive decline in APP transgenic mouse models. Alternatively, A beta aggregates may impact cognition by a mechanism that is not fully recapitulated in these BRI2-A beta mouse models.