β-Amyloid Plaques Induce Neuritic Dystrophy of Nitric Oxide-Producing Neurons in a Transgenic Mouse Model of Alzheimer's Disease

• Published in: Experimental neurology 2001-04, Vol.168 (2), p.203-212
• Main Authors: Quinn, Joseph, Davis, Forrest, Woodward, William R., Eckenstein, Felix
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Amyloid beta-Peptides - genetics; Amyloid beta-Peptides - metabolism; animal; Animals; Biological and medical sciences; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; disease models; Disease Models, Animal; Female; free radicals; Medical sciences; Mice; Mice, Transgenic; Neuroaxonal Dystrophies - metabolism; Neuroaxonal Dystrophies - pathology; Neurology; Neurons - metabolism; Neurons - pathology; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type I; oxidative; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; stress
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.2000.7598

A causative role for nitric oxide has been postulated in a number of neurodegenerative diseases. Using histochemical and immunohistochemical methods, we examined the effect of β-amyloid plaques on nitric oxide-producing cells in transgenic mice which overexpress a mutant human amyloid precursor protein (APP). In 14-month-old animals, nitric oxide synthase (NOS)-positive dystrophic neurites were observed frequently in the cerebral cortex and hippocampus of all of 16 plaque-bearing transgenic animals and in none of 16 wild-type animals. Double labeling of NOS and β-amyloid revealed that 90% of β-amyloid plaques were associated with NOS-containing dystrophic neurites. In 7-month-old animals, β-amyloid plaques were very rare, but those present were frequently associated with NOS-positive neuritic dystrophy. We conclude that β-amyloid plaques induce neuritic dystrophy in cortical neurons containing NOS in this model of AD, and hypothesize that this finding may be relevant to the mechanism of β-amyloid neurotoxicity in human AD.