The Athena Neuroscience PDAPP transgenic mice develop heavy Aβ deposits, particularly in the outer molecular layer (OML) of the dentate gyrus, a region that receives nerve projections from the entorhinal cortex. Theorizing that neuronal inputs from the entorhinal cortex might somehow drive the production of Aβ, Karen Chen and colleagues at Athena performed unilateral electrolytic lesions of the EC in mice at various ages and examined them at intervals over several months to see what effect the lesions had on Aβ deposition in the OML (Abstract 592.6). Sham lesions were performed on a group of age-matched control animals. Chen et al. reported that mice lesioned at 8.5 and 10.5 months showed a marked decrease in Aβ deposits on the lesioned side, when they were examined several weeks and months later. The effect occurred as rapidly as two weeks later (in mice lesioned at 10.5 months and examined at 11 months) and lasted at least 4.5 months (in mice lesioned at 8.5 months and examined at 13 months). Notably, mice that were lesioned at 15.5 months did not show a loss of amyloid deposition when they were sacrificed two weeks later. This intriguing but preliminary study suggests a number of possible explanations. Perhaps the lesioning triggered inflammatory processes that clear the deposits, but which become less effective with age. Or the loss of entorhinal inputs may slow down deposition sufficiently to allow endogenous clearance mechanisms to remove the preexisting deposits. It remains for follow-up studies to determine the mechanisms underlying this striking effect.-June Kinoshita.
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