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Neurobiol Aging. 1996 Sep-Oct;17(5):773-80.

Alzheimer A beta neurotoxicity: promotion by antichymotrypsin, ApoE4; inhibition by A beta-related peptides.

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Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.


Two inflammation-associated proteins found in the Alzheimer amyloid deposits-alpha 1-antichymotrypsin (ACT) and apolipoprotein E4 (apoE4)-have been shown to be genetic risk factors for the development of Alzheimer's disease and to promote the polymerization of the A beta peptide into amyloid filaments in vitro. In the present study, we show that ACT and apoE4 increase the neurotoxicity of the A beta peptide in parallel with their promotion of filament formation. Preincubation of ACT or apoE4 with small A beta-related peptides, or of apoE4 with apoE2, abrogated their subsequent ability to promote both the formation and the neurotoxicity of A beta filaments. These results indicate that ACT and apoE4 may play a stimulatory role in the formation of neurotoxic amyloid in Alzheimer's disease, and that their amyloid promoting activity can be blocked by inhibitory peptides.

[Indexed for MEDLINE]

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