Biochemical evidence for the long-tail form (Aβ1-42/43) of amyloid β protein as a seed molecule in cerebral deposits of alzheimer′s disease

A. Tamaoka, T. Kondo, A. Odaka, N. Sahara, N. Sawamura, K. Ozawa, N. Suzuki, S. Shoji, H. Mori

Research output: Contribution to journalArticle

100 Citations (Scopus)


We measured the amounts of total Aβ, Aβ1-40, and Aβ1-42/43 in brain tissues using a newly developed ELISA assay and found that the amounts of insoluble Aβ1-42/43 and insoluble Aβ1-40) were linearly related to the amount of Aβ deposits or total insoluble Aβ at their lower and higher concentrations, respectively. In an experiment to characterize the Aβ species in brain homogenates with buffered saline, we unexpectedly detected soluble Aβ which was derived from the insoluble amyloid deposits in brain tissue, indicating reversible depolymerisation of Aβ from insoluble amyloid deposits. To confirm this finding, we performed 5 consecutive washes of insoluble precipitates of AD brains with buffered saline. Both species of Aβ were found in all 5 supernatant fractions and their amounts were gradually decreased. The ratio of Aβ1-42/43/43 to Aβ1-40 was increased with the numbers of washes, indicating that Aβ1-40 existed in an exposed manner as compared to Aβ1-42/43. Thus the present finding is the first biochemical evidence that Aβ1-40 was the predominant species involved in the reversible exchanging reaction on seeding Aβ1-42/43 between the soluble and the insoluble forms (amyloid fibrils).

Original languageEnglish
Pages (from-to)834-842
Number of pages9
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - 1994 Nov 30


ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this