An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease

Nature. 1997 Oct 16;389(6652):689-95. doi: 10.1038/39522.

S D Yan ¹, J Fu, C Soto, X Chen, H Zhu, F Al-Mohanna, K Collison, A Zhu, E Stern, T Saido, M Tohyama, S Ogawa, A Roher, D Stern

Affiliations

Affiliation

1 Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA. sdy1@columbia.edu

PMID: 9338779 DOI: 10.1038/39522

Abstract

Amyloid-beta is a neurotoxic peptide which is implicated in the pathogenesis of Alzheimer's disease. It binds an intracellular polypeptide known as ERAB, thought to be a hydroxysteroid dehydrogenase Enzyme, which is expressed in normal tissues, but is overexpressed in neurons affected in Alzheimer's disease. ERAB immunoprecipitates with amyloid-beta, and when cell cultures are exposed to amyloid-beta, ERAB inside the cell is rapidly redistributed to the plasma membrane. The toxic effect of amyloid-beta on these cells is prevented by blocking ERAB and is enhanced by overexpression of ERAB. By interacting with intracellular amyloid-beta, ERAB may therefore contribute to the neuronal dysfunction associated with Alzheimer's disease.

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