Augmented senile plaque load in aged female beta-amyloid precursor protein-transgenic mice - PubMed (original) (raw)

Augmented senile plaque load in aged female beta-amyloid precursor protein-transgenic mice

M J Callahan et al. Am J Pathol. 2001 Mar.

Abstract

Transgenic mice (Tg2576) overexpressing human beta-amyloid precursor protein with the Swedish mutation (APP695SWE) develop Alzheimer's disease-like amyloid beta protein (Abeta) deposits by 8 to 10 months of age. These mice show elevated levels of Abeta40 and Abeta42, as well as an age-related increase in diffuse and compact senile plaques in the brain. Senile plaque load was quantitated in the hippocampus and neocortex of 8- to 19-month-old male and female Tg2576 mice. In all mice, plaque burden increased markedly after the age of 12 months. At 15 and 19 months of age, senile plaque load was significantly greater in females than in males; in 91 mice studied at 15 months of age, the area occupied by plaques in female Tg2576 mice was nearly three times that of males. By enzyme-linked immunosorbent assay, female mice also had more Abeta40 and Abeta42 in the brain than did males, although this difference was less pronounced than the difference in histological plaque load. These data show that senescent female Tg2576 mice deposit more amyloid in the brain than do male mice, and may provide an animal model in which the influence of sex differences on cerebral amyloid pathology can be evaluated.

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Figures

Figure 1.

Figure 1.

Tg2576 mice have an age-related increase in the percent area of the hippocampus and neocortex occupied by Aβ deposits as quantitated using a point-counting technique. Data evaluated by analysis of variance followed by a post hoc Newman-Keuls test. ***, P < 0.001, compared to all other age groups.

Figure 2.

Figure 2.

Campbell-Switzer silver AD-stained sagittal tissue sections under low (×4 objective) magnification from male (a) and female (b) Tg2576 mice representing mean percent plaque areas of 2.31% and 6.11%, respectively, at 15 months of age. The Aβ deposits are stained black or dark brown with this method. The silver stain normally turns myelinated pathways a golden brown color; these are easily distinguished from Aβ deposits under the microscope. Scale bar, 200 μm.

Figure 3.

Figure 3.

At 15 months of age, female Tg2576 mice have a threefold greater percent area of the hippocampus and neocortex occupied by senile plaques. Data evaluated by analysis of variance followed by a post hoc Newman-Keuls test. ***, P < 0.001 compared to male mice.

Figure 4.

Figure 4.

In 15-month-old Tg2576 mice, soluble and insoluble Aβ levels, measured by ELISA, were increased in females compared to males. This increase was significant for Aβ40 in both the soluble and insoluble extracts. Data evaluated by analysis of variance followed by post hoc Newman-Keuls test. *, P < 0.05; **, P < 0.01 compared to male mice.

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