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P1–105: A new screening model for neurodegenerative diseases
Author(s) -
Notsch Wolfgang,
Wronski Robert,
Hutter-Paier Birgit,
Fröhlich Kai-Uwe,
Windisch Manfred
Publication year - 2006
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.2006.05.481
Subject(s) - computational biology , neuroscience , medicine , psychology , biology
memory enhancing effects could be correlated with its effects on amyloid plaque levels in APP/PS1 transgenic mice using object discrimination and MRI imaging. Methods: We used mice expressing both APP (KM670/671NL) and PS1 (L166P) mutations on the same transgene (APP/PS1-Tg); these mice develop amyloid deposits from the age of about 2 months. Two groups of 7 APP/PS1 Tg mice were treated either with memantine (10 mg/kg; i.p.) or vehicle for a period of 4 months starting at 3 months of age. At the end of this period the Tg mice were subject to an object discrimination test. Results: We found that memantine-treated Tg mice performed the same as wild-type mice, while the performance of vehicle-treated Tg mice was significantly impaired (P .0081 one-way ANOVA). The mice were then subject to ex vivo MRI and histological examination of amyloid burden. MRI was performed in memantineand vehicle-treated Tg mice following intracarotid injection with gadolinium-DTPA-A 1-40 (co-injected with mannitol to permeabilize the blood brain barrier). For MR imaging, a gradient echo sequence sensitized to the presence of either iron or targeted magnetic contrast agent labeling plaques was used to provide both 2D T2* maps and 3D T2*-weighted image data sets with acquisition times of 55 min and 115 min, respectively. Conclusions: Analysis of whether the observed behavioral improvement by memantine can be correlated with MRI and histological evaluations of amyloid burden are underway.