Deafferentation of the hippocampus results in the induction of AT8 positive 'granules' in the rat

Hyperphosphorylated tau is a pathological hallmark of Alzheimer's disease, but the mechanisms that lead to its formation are poorly understood. To inv estigate what effect deafferentation of the hippocampus has on the phosphor ylation state of tau, we lesioned the entorhinal cortex in rats and looked for hyperphosphorylated tau in the hippocampus at various days post lesioni ng. After 7 and 21 days, small AT8-positive 'granules' appeared in the mole cular layer of the dentate gyrus on the lesioned side. No such staining was seen in the animals injected with saline. This study shows that deafferent ation leads to induction of hyperphosphorylated tau. The AT8 positive 'gran ules' seen resemble the argyrophilic grains that characterize Argyrophilic Grain disease suggesting that lesioning the perforant pathway may serve as a useful model for inducing argyrophilic grains in vivo. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.