Enhanced binding of advanced glycation endproducts (AGE) by the ApoE4 isoform links the mechanism of plaque deposition in Alzheimer's disease

doi:10.1016/S0304-3940(97)00266-8

Neuroscience Letters

Volume 226, Issue 3, 2 May 1997, Pages 155-158

https://doi.org/10.1016/S0304-3940(97)00266-8 Get rights and content

Abstract

Alzheimer's disease (AD) brains contain high levels of advanced glycation endproducts (AGEs). Double immunostaining using anti-AGE and anti-apolipoprotein E (apoE) antibodies demonstrated that AGEs co-localized to a very high degree with apoE. We examined the binding of apoE to in vitro-prepared AGE-bovine serum albumin (AGE-BSA), using Western ligand blot analysis. ApoE exhibited AGE-specific binding activity in the presence of excess native BSA, with the dimeric form of apoE binding better than the monomeric form. Other apolipoproteins including apo A1, B, CI and CII, and serum β₂-microglobulin, did not bind AGE-BSA. ApoE4 exhibited a 3-fold greater AGE-binding activity than the apoE3 isoform. These results suggest that apoE may participate in aggregate formation in the AD brain by binding to AGE-modified plaque components. It is possible that enhanced binding of apoE4 might have pathogenic consequences in vivo.

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Acknowledgements

The authors thank Dr. Michael Yamin for critical comments and Dr. Richard Bucala for providing anti-AGE antibody. This study is partially supported by awards from American Diabetes Association and Institute for Advanced Studies in Immunology and Aging to Y.M.L.

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Enhanced binding of advanced glycation endproducts (AGE) by the ApoE4 isoform links the mechanism of plaque deposition in Alzheimer's disease

Abstract

Section snippets

Acknowledgements

Neurobiol. Aging

Neurosci. Lett.

J. Biol. Chem.

Life. Sci.

Alzheimer's disease, risky apolipoprotein in brain

Nature

Tau protein from Alzheimer's disease patients is glycated at its tubulin-binding domain

J. Neurochem.

Macrophages synthesize and secrete a 25-kilodalton protein that binds insulin-like growth factor-I

J. Immunol.

Prevention of cardiovascular and renal pathology of aging by the advanced glycation inhibitor aminoguanidine

Proc. Natl. Acad. Sci. USA