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NeuroScience Associates

Campbell-Switzer Alzheimer Silver Stain Method

Applications:
  • Stain for Alzheimer pathology.
  • Applicable for humans and transgenic (Alzheimer) models.
Advantages:
  • Capable of staining both Alzheimer plaques and tangles.
  • Provides capability to assess a drug’s capability to prevent diffuse plaques from maturing.
  • Less expensive to execute than the antibody method: Large quantities of sections are processed the same day with no overnight antibody incubation required.
  • Yields high contrast images amenable to densitometric analysis.
  • Reveals multiple Alzheimer features, while antibody stains are feature specific.

 

 

Specifications:

Human brain section of an Alzheimer patient with the Campbell-Switzer Alzheimer plaque stain applied the Campbell-Switzer stain was developed to be a high contrast stain that easily permits the image analysis of the neuritic plaques and neurons with neurofibrillary tangles that are the hallmark pathologic features of Alzheimer disease. Both diffuse and amyloid core plaques are displayed. When combined with MultiBrain® Technology, we are able to process very large freeze-cut free floating sections that are ideal for qualitative and quantitative image analysis. Traditional stains, such as the Bielschowsky method, were designed exclusively for sections cut from paraffin blocks. Using the Campbell-Switzer method on freeze-cut free floating sections allows for a superior staining process as well as capacity for staining larger sections (Campbell-Switzer may be applied to paraffin sections as well). Plaques are revealed in high contrast against a pale background, ideal for image analysis.

Campbell-Switzer Method Applied to Human Sections:

In the hemisphere of this Alzheimer disease case (right and below), the pathology is very advanced as indicated by the high density of plaques in the cortex as well as striatum and thalamus. In spite of this density, relatively few plaques have amyloid cores. In addition, the neurons with neurofibrillary tangles are in the hippocampus and subiculum.

Campbell-Switzer Applied to a Transgenic Mouse

The Campbell-Switzer stain was designed for human sections. As transgenic mouse models were developed, NSA adapted the stain to work equally well for mice. Advances in biochemical and genetic characterization of the amyloid associated with Alzheimer pathology and in transgenic techniques have allowed the creation of transgenic mice that develop amyloid plaques very similar to those found in human Alzheimer Pathology.

APP Mouse Model

The APP transgenic mouse has been the most popularly used model with neuritic plaques conspicuously displayed by the age of 12-13 months of age.

PS-1/APP Mouse Model

The development of transgenic mice that are doubly transgenic for APP and presenilin-1 (PS-1) yielded mice that developed plaques at a much earlier age than the singly transgenic APP mouse.

The burden of plaques in both transgenic models can be readily assessed in sections stained with the Campbell-Switzer method using modern image analysis techniques.

Helpful links:

FAQ regarding silver stains:

Are silver stains all the same?

No. There are numerous silver staining protocols, each tailored to reveal specific features. "Silver Stains" are as unique as any other stain in that they are each specifically designed to stain a particular feature. Silver simply refers to the staining agent (Silver) which stains the designated feature black.

Does the Campbell-Switzer stain show the same features as the disintegrative degeneration stain?

No. Each method reveals a different set of features. The Campbell-Switzer method reveals the neuritic plaques and tangles of Alzheimer's pathology. The disintegrative degeneration stain shows the products of neuronal disintegrative degeneration.

How do the plaques revealed by the Campbell-Switzer stain in transgenic mouse models compare with staining using antibodies against different forms of amyloid?

Some antibodies show only a subset of plaques revealed by the Campbell-Switzer method, while others appear to be a one to one match. The Campbell-Switzer stain is unique in its ability to differentiate its staining of immature (diffuse) and mature (congophilic) plaques, allowing researchers a unique observational capability.

 

For further reference, please see: Stains