Amyloid plaque cores were purified from Alzheimer disease brain tissue. Plaque core proteins were solubilized in formic acid which upon dialysis against guanidinium hydrochloride (GuHCl) partitioned into soluble (approximately 15%) and insoluble (approximately 85%) components. The GuHCl-soluble fraction contained beta-amyloid1-40, whereas the GuHCl-insoluble fraction was fractionated into six components by size exclusion HPLC: S1 (> 200 kDa), S2 (200 kDa), S3 (45 kDa), S4 (15 kDa), S5 (10 kDa), and S6 (5 kDa). Removal of the GuHCl reconstituted 10-nm filaments composed of two intertwined 5-nm strands. Fractions S5 and S6 also yielded filamentous structures when treated similarly, whereas fractions S1-S4 yielded amorphous aggregates. Chemical analysis identified S4-S6 as multimeric and monomeric beta-amyloid. Immunochemical analyses revealed alpha 1-antichymotrypsin and non-beta-amyloid segments of the beta-amyloid precursor protein within fractions S1 and S2. Several saccharide components were identified within plaque core protein preparations by fluorescence and electron microscopy, as seen with fluorescein isothiocyanate- and colloidal gold-conjugated lectins. We have shown previously that this plaque core protein complex is more toxic to neuronal cultures than beta-amyloid. The non-beta-amyloid components likely mediate this additional toxicity, imposing a significant influence on the pathophysiology of Alzheimer disease.