Augmented Senile Plaque Load in Aged Female β-Amyloid Precursor Protein-Transgenic Mice

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.

Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice

“…Consistently, the plaque load in Tg2576 mice showed the same intersexual disparity (31). Although causes for this are unknown, our studies suggest that female-restricted increases of synaptic vesicle zinc may play a crucial role in the sexually disparate accumulation of amyloid plaques in Tg2576 mice.…”

Accelerated amyloid deposition, neurofibrillary degeneration and neuronal loss in double mutant APP/tau transgenic mice

“…This observation, previously noted by others in the Tg2576 line (APP sw ) (Callahan et al, 2001), points to the importance of gender in amyloid production/deposition and highlights the need to take this variable into account in the design of studies carried out on these mice, and possibly on other Tg mouse models of brain amyloidogenesis (Wang et al, 2003).…”

Vitamin E reduces amyloidosis and improves cognitive function in Tg2576 mice following repetitive concussive brain injury

“…At 11 months of age, Tg2576 female mice were randomized to receive either a regular chow or chow supplemented with 2 IU/g diet vitamin E. The choice of using only female mice was based on previous work showing that in this animal model females exhibit a more consistent and greater amount of Ab formation and deposition than males (Callahan et al 2001). Preliminary experiments demonstrated that the selected dose of vitamin E significantly reduces in vivo LPO (Praticò et al 1998a).…”