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4‐Hydroxynonenal‐Derived Advanced Lipid Peroxidation End Products Are Increased in Alzheimer's Disease
Author(s) -
Sayre Lawrence M.,
Zelasko Dawn A.,
Harris Peggy L. R.,
Perry George,
Salomon Robert G.,
Smith Mark A.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68052092.x
Subject(s) - senile plaques , lipid peroxidation , 4 hydroxynonenal , oxidative stress , hippocampal formation , neurotoxicity , alzheimer's disease , chemistry , pathology , neuroscience , biochemistry , medicine , endocrinology , biology , disease , toxicity
Recent studies have demonstrated oxidative damage is one of the salient features of Alzheimer's disease (AD). In these studies, glycoxidation adduction to and direct oxidation of amino acid side chains have been demonstrated in the lesions and neurons of AD. To address whether lipid damage may also play an important pathogenic role, we raised rabbit antisera specific for the lysine‐derived pyrrole adducts formed by lipid peroxidation‐derived 4‐hydroxynonenal (HNE). These antibodies were used in immunocytochemical evaluation of brain tissue from AD and age‐matched control patients. HNE‐pyrrole immunoreactivity not only was identified in about half of all neurofibrillary tangles, but was also evident in neurons lacking neurofibrillary tangles in the AD cases. In contrast, few senile plaques were labeled, and then only the dystrophic neurites were weakly stained, whereas the amyloid‐β deposits were unlabeled. Age‐matched controls showed only background HNE‐pyrrole immunoreactivity in hippocampal or cortical neurons. In addition to providing further evidence that oxidative stress‐related protein modification is a pervasive factor in AD, the known neurotoxicity of HNE suggests that lipid peroxidation may also play a role in the neuronal death in AD that underlies cognitive deficits.