Neuritic Plaque Amyloid in Alzheimer's Disease Is Highly Racemized

Abstract

Neuritic plaque core amyloid protein in Alzheimer's disease brain tissue was investigated for the extent of amino acid racemization. Long-lived human proteins exhibit racemization of certain amino acids over the course of a human lifetime. Purified core amyloid was found to contain relatively large proportions of D-aspartate and D-serine, suggesting that neuritic plaque amyloid is derived from a long-lived precursor protein. Alternatively, racemization of protein amino acids may be abnormally accelerated in Alzheimer's disease.

A Seed for Alzheimer Amyloid in the Brain

“…In this study, it remains to be clarified why 4396C did not immunostain plaques in which the ends of amyloid fibrils were supposed to exist. Possible explanations for this failure are as follows; first, the number of epitopes that can be recognized by the antibody may be limited, as was clearly indicated by immunoelectron microscopy using fibrils; second, we may have lost their immunoreactivities because of their higher susceptibility to treatment in immunohistochemistry than GA␤; and third, the ends of amyloid fibrils may have been masked or modified in the brain (Shapira et al, 1988;Roher et al, 1993).…”

Racemization: Its Biological Significance on Neuropathogenesis of Alzheimer's Disease.

“…In Alzheimer's disease, Shapira and colleagues investigated the racemization of amyloid core protein, myelin basic protein (MBP), and other human proteins, demonstrating that Received July 18, 1994; revision accepted for publication September 5, 1994. 251 4.57% ± 1.24 (n = 4) of aspartate in amyloid core protein was D-Asp compared to 7.46%±O.09 (n = 6) in human MB P or 1.99%±O.24 (n=3) in human hair (Shapira et al 1988). Amyloid core protein is less racemized than MBP, but apparently more racemized than other proteins included in hair, muscle, and tendon (Shapira et al 1988).…”

“…251 4.57% ± 1.24 (n = 4) of aspartate in amyloid core protein was D-Asp compared to 7.46%±O.09 (n = 6) in human MB P or 1.99%±O.24 (n=3) in human hair (Shapira et al 1988). Amyloid core protein is less racemized than MBP, but apparently more racemized than other proteins included in hair, muscle, and tendon (Shapira et al 1988). Amyloid /3 protein (Af), composed of 39 to 43 amino acids, is produced from a large receptor-like transmembrane precursor termed amyloid precursor protein (APP).…”

In vivo conversion of racemized β‐amyloid ([D‐Ser26]Aβ1–40) to truncated and toxic fragments ([D‐Ser26]Aβ25–35/40) and fragment presence in the brains of Alzheimer's patients

“…Racemization of Ser and Asp residues in A␤ peptides is one of the typical age-dependent modifications occurring in AD brains (Shapira et al, 1988;Roher et al, 1993;Saido, 1998;Lowenson et al, 1999). In contrast to fibrillar A␤1-40, A␤1-40 racemized at (Kaneko et al, 2001).…”