Augmented senile plaque load in aged female beta-amyloid precursor protein-transgenic mice.
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.
Callahan
M J
MJ
Neuroscience Therapeutics, Pfizer Global Research and Development, Ann Arbor Laboratories, 2800 Plymouth Rd., Ann Arbor, MI 48105, USA. michael.callahan@pfizer.com
Lipinski
W J
WJ
Bian
F
F
Durham
R A
RA
Pack
A
A
Walker
L C
LC
D000375:Aging; D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019579:Neocortex / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000096:biosynthesis; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D012737:Sex Factors
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)