Morphological and Biochemical Analyses of Amyloid Plaque Core Proteins Purified from Alzheimer Disease Brain Tissue

Alex E. Roher, Kenneth C. Palmer, Edward C. Yurewicz, Melvyn J. Ball, Barry D. Greenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Abstract— Amyloid plaque cores were purified from Alzheimer disease brain tissue. Plaque core proteins were solubilized in formic acid which upon dialysis against guan‐idinium hydrochloride (GuHCI) partitioned into soluble (∼15%) and insoluble (∼85%) components. The GuHCI‐soluble fraction contained β‐amyloid1‐40, whereas the GuHCI‐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 GuHCI 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 β‐amyloid. Immunochemical analyses revealed α1‐antichymotrypsin and non‐β‐amyloid segments of the β‐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 fluores‐cein isothiocyanate‐and colloidal gold‐conjugated lectins. We have shown previously that this plaque core protein complex is more toxic to neuronal cultures than β‐amyloid. The non‐β‐amyloid components likely mediate this additional toxicity, imposing a significant influence on the pathophysiology of Alzheimer disease.

Original languageEnglish (US)
Pages (from-to)1916-1926
Number of pages11
JournalJournal of Neurochemistry
Volume61
Issue number5
DOIs
StatePublished - Nov 1993
Externally publishedYes

Keywords

  • accharides
  • euritic plaque
  • α ‐Antichy‐motrypsin
  • β‐Amyloi
  • β‐Amyloid precursor protein

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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