Advanced glycation end products contribute to amyloidosis in Alzheimer disease.

来自 NCBI

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阅读量：

106

作者：

Vitek，M.，P.，Bhattacharya，K.，Glendening，J.，M.，Stopa，E.

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摘要：

Alzheimer disease (AD) is characterized by deposits of an aggregated 42-amino-acid β-amyloid peptide (βAP) in the brain and cerebrovasculature. After a concentration-dependent lag period during in vitro incubations, soluble preparations of synthetic βAP slowly form fibrillar aggregates that resemble natural amyloid and are measurable by sedimentation and thioflavin T-based fluorescence. Aggregation of soluble βAP in these in vitro assays is enhanced by addition of small amounts of pre-aggregated β-amyloid "seed" material. We also have prepared these seeds by using a naturally occurring reaction between glucose and protein amino groups resulting in the formation of advanced "glycosylation" end products (AGEs) which chemically crosslink proteins. AGE-modified βAP-nucleation seeds further accelerated aggregation of soluble βAP compared to non-modified "seed" material. Over time, nonenzymatic advanced glycation also results in the gradual accumulation of a set of posttranslational covalent adducts on long-lived proteins in vivo. In a standardized competitive ELISA, plaque fractions of AD brains were found to contain about 3-fold more AGE adducts per mg of protein than preparations from healthy, age-matched controls. These results suggest that the in vivo half-life of β-amyloid is prolonged in AD, resulting in greater accumulation of AGE modifications which in turn may act to promote accumulation of additional amyloid.

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关键词：

Neurobiology β-Amyloid Peptide Aggregation Nucleation-Dependent Kinetics Seed Structure and Function

DOI：

10.1073/pnas.91.11.4766

被引量：

2182

年份：

1994