4-Hydroxy-2-Nonenal Pyrrole Adducts in Human Neurodegenerative Disease

• Published in: Journal of neuropathology and experimental neurology 1997-08, Vol.56 (8), p.866-871
• Main Authors: MONTINE, K S, KIM, P J, OLSON, S J, MARKESBERY, W R, MONTINE, T J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Aldehydes - metabolism; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Apolipoprotein E3; Apolipoprotein E4; Apolipoproteins E - genetics; Biological and medical sciences; Brain; Brain - metabolism; Brain - pathology; Brain damage; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA Adducts - metabolism; Female; Genotype; Homozygote; Humans; Lipid peroxidation; Male; Medical research; Medical sciences; Middle Aged; Nerve Degeneration; Nervous system diseases; Nervous System Diseases - genetics; Nervous System Diseases - metabolism; Neurology; Pyrroles - metabolism
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/00005072-199708000-00004

Increasing age and inheritance of the ∈4 allele of apolipoprotein E (APOE4) are significant risk factors for sporadic and late onset familial Alzheimer disease (AD); however, the mechanisms by which either leads to AD are unknown. Numerous studies have associated advancing age with increased indices of oxidative challenge to brain, and with still further increased oxidative damage to relevant brain regions in AD patients. A major consequence of oxidative damage to brain is lipid peroxidation with production of the neurotoxic metabolite 4-hydroxy-2-nonenal (HNE). HNE reacts with protein to yield several adducts, including a pyrrole adduct that forms irreversibly in biological systems. Previously, we have shown in a small number of AD and control patients that HNE pyrrole adduct antiserum is immunoreactive with neurofibrillary tangles (NFT), and that this reactivity was significantly associated with inheritance of APOE4. Others have confirmed this pattern of immunoreactivity in AD brain but did not observe an association with APOE4. Herein, we have expanded the study group to 19 AD patients homozygous for APOE4 or APOE3, as well as 30 patients with other neurodegenerative diseases, including diffuse Lewy body disease, Pickʼs disease, progressive supranuclear palsy, Parkinsonʼs disease, and human immunodeficiency virus-1 encephalitis. HNE pyrrole adduct immunoreactivity on NFT in AD patients was strongly associated with APOE4 homozygosity. With the exception of rare immunoreactive Pick bodies in one case of Pickʼs disease, no other structure was recognized by HNE pyrrole adduct antiserum in this series of patients. We propose that there is a significant difference between the interaction of apoE3 and apoE4 with lipid peroxidation in the brains of AD patients.