New temperature modification makes the Bielschowsky silver stain reproducible

The Bielschowsky silver impregnation can be used as a single stain for the diagnosis of Alzheimer's disease. It impregnates both the amyloid and neuritic components of the senile plaques and it reliably stains neurofibrillary tangles. However, we find that the stain is highly sensitive to changes of the ambient temperature. Since the diagnostic criteria for Alzheimer's disease rely on a semi-quantitative assessment of neuritic plaques and neurofibrillary tangles the reproducibility of the Bielschowsky stain is important. In this study we compare three different modifications of the Bielschowsky stain with the methenamine silver stain and with immunohistochemistry for the beta-amyloid and the hyperphosphorylated tau proteins. We found that the most reliable and easily reproducible modification of the Bielschowsky silver impregnation is the one that uses incubations at 5 degrees C.