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 investigate what effect deafferentation of the hippocampus has on the phosphorylation state of tau, we lesioned the entorhinal cortex in rats and looked for hyperphosphorylated tau in the hippocampus at various days post lesioning. After 7 and 21 days, small AT8-positive 'granules' appeared in the molecular layer of the dentate gyrus on the lesioned side. No such staining was seen in the animals injected with saline. This study shows that deafferentation leads to induction of hyperphosphorylated tau. The AT8 positive 'granules' 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.