Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro

Am J Pathol. 1994 Nov;145(5):1030-5.


Numerous studies have established a linkage between the apolipoprotein (apo) E4 allele and late-onset Alzheimer's disease. It remains unclear if apo E plays a direct role in the pathogenesis of Alzheimer's disease and what, if any, are its significant interactions with amyloid beta (A beta) and tau. Apo E has been found immunohistochemically in all types of amyloid deposits and apo E fragments have been isolated from amyloid. Furthermore, apo E has been shown to bind soluble A beta. It has been proposed that apo E acts to promote and/or modulate A beta fibril formation. It is well established that peptides homologous to A beta will form amyloid-like fibrils in solution. With the use of electron microscopy and a thioflavin T assay for fibril formation we found that apo E and apo E4 in particular enhance this spontaneous fibrillogenesis of A beta peptides under the in vitro conditions used. These in vitro data suggest that the apo E4 isoform is a risk factor for Alzheimer's disease that acts to accelerate a process that can occur in its absence.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism
  • Apolipoproteins E / pharmacology*
  • Humans
  • In Vitro Techniques
  • Neurofibrillary Tangles / drug effects
  • Neurofibrillary Tangles / metabolism*
  • Neurofibrillary Tangles / ultrastructure
  • Peptides


  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Peptides