Magnetic resonance spectroscopic analysis of Alzheimer's disease mouse brain that express mutant human APP shows altered neurochemical profile.
Transgenic mice that express mutant human amyloid precursor protein (APPTg2576) develop beta-amyloid (Abeta) plaques throughout the cortex starting at 10-12 months of age. We examined the neurochemical profile of APPTg2576 mice using in vitro and in vivo magnetic resonance spectroscopy (MRS); gross abnormalities using magnetic resonance imaging (MRI) and plaque distribution; size and number using immunohistochemistry. Transgenic mice were anesthetized with halothane and scanned at 4.7 T using T2-weighted imaging and in vivo MRS of frontal cortex. In vitro MRS was run from brain extracts of frontal cortex in both APP and wild-type mice. Mice were also perfused and brains were collected and cut for immunohistochemistry. We found that N-acetylaspartate (NAA), glutamate and glutathione were decreased by 17%, 22% and 36%, respectively, in the cerebral cortex of APP transgenic mice at 19 months of age when Abeta deposits are widespread. Taurine was increased 21% compared to wild-type. Decreased levels of NAA and increased levels of taurine are consistent with decreased neuronal viability and increased glial volume, and are similar to findings of decreased NAA and increased myo-inositol in human Alzheimer's disease (AD) brains. Correlation between the severity of Abeta deposition and altered neurochemical profile remains to be studied. Nevertheless, the altered neurochemical profile may be a valuable marker to test therapeutics in this mouse model.
Dedeoglu
Alpaslan
A
Geriatric Research Education and Clinical Center, Bedford Veterans Administration Medical Center, MA 01730, USA. dedeoglu@bu.edu
Choi
Ji-Kyung
JK
Cormier
Kerry
K
Kowall
Neil W
NW
Jenkins
Bruce G
BG
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic
D016564:Amyloid beta-Protein Precursor