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O4‐03‐06: Calcium binding protein Secretagogin expression in wild type and transgenic tau (P301L) mice
Author(s) -
Attems Johannes,
GrosingerQuass Magdalena,
Nitsch Roger,
Maj Magdalena,
Wagner Ludwig,
Jellinger Kurt,
Heikenwalder Mathias
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.05.536
Subject(s) - olfactory bulb , hippocampus , genetically modified mouse , transgene , medicine , endocrinology , biology , immunohistochemistry , biochemistry , central nervous system , gene
conditions of both diseases, and characterized their phenotypes longitudinally. Methods: We cross-bred amyloid precursor protein transgenic mice (APP-Tg) with two types of diabetes model mice, ob/ob and NSY mouse. APP-Tg crossed with ob/ob mouse was fed normal chow. APP-Tg crossed with NSY mouse was divided into three diet groups, and fed high-fat diet, high-sucrose diet and normal chow. We characterized metabolic phenotypes (body weight, blood glucose and insulin levels, glucose and insulin tolerance) and AD-pathology (cognitive function and brain Ab load) of these model animals longitudinally. Results: Two types of transgenic mice (APP-ob/ob and APP-NSY mouse) with pathological conditions of both diabetes and AD were successfully generated. Compared with APP-Tg, APPob/ob mice gained more body weight and developed marked hyperglycemia, hyperinsulinemia and glucose intolerance. These metabolic changes were associated with the very early (at the age of 2 months) manifestation of memory impairment. Surprisingly, this exacerbation of memory impairment was not accompanied by an increase in the Ab protein levels in the brain compared with APP-Tg. Furthermore, APP-ob/ob mice showed more prominent metabolic dysregulation compared with ob/ob mice. APP-NSY mice also showed early manifestation of cognitive dysfunction at the age of 3-month, without detectable amyloid plaques in the brain. Moreover, 5-month high-calorie feeding induced further exacerbation of memory impairment. Conclusions: We successfully generated two types of novel transgenic mouse models which show pathological phenotypes both of diabetes and AD. Exacerbation of memory impairment without an increase in Ab load in the brain of these diabetic APP-Tg implies the role of diabetic conditions on Ab-mediated neuronal dysfunction. Early manifestation of AD-like cognitive dysfunction of these animals provides a valuable model for drug development or screening for AD. Our findings also suggest the possibility that AD pathology could exacerbate metabolic phenotypes of diabetes.