Advanced glycation end products contribute to amyloidosis in Alzheimer disease.

• DOI: 10.1073/pnas.91.11.4766
• Publication Date: 2006-05-31T12:47:09Z
• Authors: M P Vitek; K Bhattacharya; J M Glendening; E Stopa; H Vlassara; R Bucala; K Manogue; A Cerami
• Keywords: Thioflavin; Amyloid (mycology); Amyloid beta; P3 peptide

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