Format

Send to

Choose Destination
Neuroscience. 2001;104(3):609-13.

Fibrillar beta-amyloid evokes oxidative damage in a transgenic mouse model of Alzheimer's disease.

Author information

1
Dementia Research Group, Nathan Kline Institute/New York University Medical Center, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.

Abstract

Beta-amyloid is one of the most significant features of Alzheimer's disease, and has been considered to play a pivotal role in neurodegeneration through an unknown mechanism. However, it has been noted that beta-amyloid accumulation is associated with markers of oxidative stress including protein oxidation (Smith et al., 1997), lipid peroxidation (Mark et al., 1997; Sayre et al., 1997), advanced glycation end products (Smith et al., 1994), and oxidation of nucleic acids (Nunomura et al., 1999). Furthermore, studies from cultured cells have shown that beta-amyloid leads to an increase in hydrogen peroxide levels (Behl et al., 1994), and the production of reactive oxygen intermediates (Harris et al., 1995). Taken together, this evidence supports the idea that beta-amyloid plays a key role in oxidative stress-evoked neuropathology. In this study, we examined the induction of oxidative stress in response to amyloid load in a mouse model of Alzheimer's disease. The mice carrying mutant amyloid precursor protein and presenilins-1 (Goate et al., 1991; Hardy, 1997), develops beta-amyloid deposits at 10-12 weeks of age and show several features of the human disease (Holcomb et al., 1998; Matsuoka et al., 2001; McGowan et al., 1999; Takeuchi et al., 2000; Wong et al., 1999). Both 3-nitrotyrosine and 4-hydroxy-2-nonenal (protein and lipid oxidative stress markers, respectively) associate strongly with fibrillar beta-amyloid, but not with diffuse (thioflavine S negative) beta-amyloid, and the levels increase in relation to the age-associated increase in fibrillar amyloid load.From these data we suggest that fibrillar beta-amyloid is associated with oxidative damage which may influence disease progression in the Alzheimer's disease brain.

PMID:
11440793
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center