title: Chemical and immunological heterogeneity of fibrillar amyloid in plaques of Alzheimer's disease and Down's syndrome brains revealed by confocal microscopy.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Schmidt
authors.forename: K A
authors.initials: KA
authors.lastname: Robinson
authors.forename: V M
authors.initials: VM
authors.lastname: Lee
authors.forename: J Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000682:Amyloid / Q000276:immunology* / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004314:Down Syndrome / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008875:Middle Aged
chemical_list: D000682:Amyloid