A Modification of the Bielschowsky Silver Stain for Alzheimer Neuritic Plaques: Suppression of Artifactual Staining by Pretreatment with Oxidizing Agents

Abstract

The Bielschowsky silver method has been the most commonly-used histological stain for demonstrating the neuritic plaques and neurofibrillary tangles that define Alzheimers disease (AD). The stain has been critical to providing a common measure allowing large clinicopathological correlation studies that have demonstrated statistically significant and independent contributions of both lesion types to cognitive impairment and dementia. The continuing relevance of neuritic plaques, and the Bielschowsky stain as the method of choice for their demonstration, is also indicated by its use as the US Food and Drug Administration (FDA) \"standard of truth\" for autopsy confirmation of the validity of PET amyloid imaging agents. Many modifications of the Bielschowsky stain have been published but it is still known to frequently generate artifactual staining that at times mimics the appearance of amyloid plaques. In this study we found that pretreatment with oxidizing agents prior to the initial incubation in silver nitrate eliminates these artifacts and reduces the commonly observed high background staining. This new method may be valuable for Alzheimers disease (AD) researchers and neuropathologists.