Water-soluble Aβ (N-40, N-42) oligomers in normal and Alzheimer disease brains

Yu Min Kuo, Mark R. Emmerling, Carmen Vigo-Pelfrey, Timothy C. Kasunic, Joel B. Kirkpatrick, Geoffrey H. Murdoch, Melvyn J. Ball, Alex E. Roher

Research output: Contribution to journalArticlepeer-review

532 Citations (Scopus)

Abstract

Ultracentrifugation and graded molecular sieving, as well as a sensitive sandwich enzyme-linked immunosorbent assay were used to isolate and quantitate the amounts of water-soluble oligomers of β amyloid (Aβ) peptides N-40 and N-42 in cerebral cortex of normal and Alzheimer disease (AD) brains. AD brains contained 6-fold more water-soluble Aβ (wsAβ) than control brains. The majority of water-soluble peptides in most AD cases was Aβ N-42, representing 12 times the amount found in control brains. The wsAβ was present in the form of monomers and oligomers ranging from less than 10 kDa to greater than 100 kDa. The amount of wsAβ N-42 in AD brains is about 50 times greater than the level of soluble Aβ N-42 found in the CSF of AD patients. This disparity may be due to the rapid association of wsAβ N-42 into fibrillar deposits and/or to the integrity of the anatomical barriers which separate the two extracellular spaces. In this paper, we consider soluble any form of Aβ which has not yet polymerized into its insoluble, filamentous form. This includes both the newly synthesized forms of Aβ and those peptides which may be loosely attached to insoluble filaments but which can, nevertheless, still be considered soluble. It has been previously shown that, once it has aggregated into its filamentous form, the Aβ peptides are resistant to disaggregation and degradation by a number of denaturing agents and aqueous buffers containing proteolytic enzymes. Therefore, it is likely that the water-soluble Aβ peptides we quantified are precursors to its insoluble, filamentous form. Consequently, reducing the levels of soluble Aβ in AD brains could have profound effects on AD pathophysiology.

Original languageEnglish
Pages (from-to)4077-4081
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number8
DOIs
Publication statusPublished - 1996 Feb 23

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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