Chemical and immunological heterogeneity of fibrillar amyloid in plaques of Alzheimer's disease and Down's syndrome brains revealed by confocal microscopy.

Amyloid beta peptides (A beta) are deposited in the brains of Alzheimer's disease (AD) and elderly Down's syndrome (DS) patients in a variety of amyloid plaques. Among these are classical plaques composed of a spherical core and corona. Analyzing AD tissue sections single and double stained with anti-A beta antibodies and thioflavin S (thioS) by bright field, fluorescence, and confocal microscopy revealed that spherical plaque cores consist of a thioS-positive center and an anti-A beta antibody immunoreactive rim. This indicates that there is a fibrillar form of amyloid that is thioS positive but not immunoreactive with anti-A beta antibodies. In contrast, classical plaques in DS patients have irregular cores that are thioS positive as well as anti-A beta immunoreactive. In addition, a subset of plaques in both DS and AD patients have a distinct "fibrous" appearance when stained with thioS, but are amorphous when immunostained. These findings suggest that anti-A beta antibodies and thioS stain similar; as well as different forms of fibrillar amyloid. A beta may become thioS positive by interacting with one or more of its known molecular chaperons, and this may be important for the pathogenesis of AD, given that thioS-positive A beta deposits are associated with neuritic and synaptic damage.