Methenamine Silver Stain Impregnates Amyloid-related Components of Senile Plaques in the Alzheimer Brains as Clearly as βprotein Immunostaining

Abstract

We developed a new type of methenamine silver (MS) stain for senile plaques (SP) on paraffin-embedded tissue sections. This method is a modification of both Gomori's methenamine silver nitrate, and Jone's periodic acid-methenamine silver (PAM) stains. We omitted chemical preoxidation by either periodic acid in the PAM stain or chromic acid in Gomori's stain, and determined the best condition of silver solution for SP. This resulted in selective staining of SP and amyloid angiopathy, because capillary basement membranes, corpora amylacea, macrophage granules, and nerve cell pigments remained unstained. The argyrophilia of SP was not affected by pretreatment with aldehyde blocking reagents. In comparison with βprotein immunostain, our MS stain showed almost the same staining pattern as that of the βprotein immunostain. Moreover, the argyrophilia of SP was selectively abolished by formic acid pretreatment, which has been shown to destroy β-pleated sheet structure of amyloid, suggesting that our MS stain impregnates amyloid-related components of SP. Our MS stain is a new, rapid, easy, and reliable method, and sensitive enough for routine or screening studies of the SP.