Beta-amyloid and oxidative stress in the pathogenesis of Alzheimer's Disease (original) (raw)

Abstract

Another common pathological feature of the AD brain is the presence of amyloid deposits in and around blood vessels known as congophilic amyloid angiopathy. A common feature of these lesions is the presence of amyloid deposits which have similar secondary structures and thus take up the dye Congo red which characteristically stains amyloid proteins having ␤-pleated sheets. N eurofibrillary tangles Neurofibrillary tangles (NFT) are found within the nerve cells. They are found in greater numbers in AD patients, primarily in regions associated with memory and other intellectual functions. A major component of the tangles is a protein called tau. Tau is responsible for directing assembly and disassembly of microtubules. In the NFT the tau protein is abnormally phosphorylated. It is thought that excessive phosphorylation of the tau protein may prevent it from stabilizing microtubules, which accumulate to form amyloid fibrils within the nerve cell, thereby causing breakdown in the structural framework. The NFT is formed later than the senile plaque and is thought to result from the toxic action of the extracellular amyloid. Amyloid plaques There is extensive variation in amyloid plaque morphology. However, comprehensive histological analysis has identified two categories of plaques: diffuse and neuritic (Yamaguchi et al., 1988; Wisniewski et al., 1989; Schmidt et al., 1994). Diffuse plaques, which reflect newly formed deposits, do not elicit gliosis and are thought to be benign. They are abundant in the brains of some non-demented elderly individuals as well as in the brains of AD patients (Yamaguchi et al., 1988; Wisniewski et al., 1989; Schmidt et al., 1994). Neuritic plaques are focal, spherical collections of dilated, tortuous, silver-staining neuritic processes (dystrophic neurites) surrounding a central amyloid core. They are very common in AD patients. These plaques contain abundant amyloid fibrils and are intensely stained by Thioflavin S, Congo red as well as several different types of silver stains (Trojanowski et al., 1993). Neuritic plaques are not common in normal ageing. Hence, this form of amyloid plaque is a better indicator of AD than the diffuse plaque. The major protein component of both the diffuse and neuritic plaque is a 4 kDa peptide termed ␤-amyloid. ␤-Amyloid and Amyloid Precursor Protein ␤-Amyloid (A␤) A␤ is a 4 kDa hydrophobic protein, composed of 39-43 amino acids. A␤ was discovered when it was isolated from the meningeal blood vessels (Glenner and Wong, 1984) and the cores of the amyloid plaques (Masters et al., 1985) of AD patients.

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