Gender dependent APP processing in a transgenic mouse model of Alzheimer's disease.
Epidemiological studies have reported a higher prevalence and incidence of Alzheimer's disease (AD) in women. The biochemical basis for this gender-disparate susceptibility is unknown. A gender effect on AD-typical plaque pathology has been shown in APP transgenic mouse models of AD. Female mice elicit higher plaque load than male mice. In an effort to analyze gender-dependent APP processing during postnatal development, we examined APP transgenic mice at time points prior to plaque deposition. At 14 weeks of age there was a significant elevation of C99 and Abeta in female mice compared to males. Furthermore we observed a slight decrease of BACE-activity in male mice as well as higher cerebral manganese levels in females. Although the decline in estrogen levels due to menopause in female patients is still discussed to be a risk factor for AD our results implicates that additional factors like modified BACE-activity or metal levels may contribute to the higher prevalence and incidence of AD in females.
Schäfer
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Department of Psychiatry, Division of Neurobiology, Saarland University, Homburg/Saar, Germany. thomas.bayer@uniklinik-saarland.de
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Multhaup
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Bayer
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D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004967:Estrogens / Q000378:metabolism; D005260:Female; D008297:Male; D008345:Manganese / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D015854:Up-Regulation / Q000502:physiology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D004967:Estrogens; D008345:Manganese; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse