[Abstract Title]. - Society for Neuroscience

invasive in vivo magnetic resonance imaging and spectroscopy (MRI, MRS) have been recently
employed for CNS diseases as translational tools. In human AD, metabolic changes including
increase in myo-inositol and decrease in N-acetyl-aspartate (NAA) have been reported. Similarly
MRI has been applied to demonstrate brain atrophy. Here we characterize the Tg2576 mouse
model of AD, carrying a mutated form of the human amyloid precursor protein and exhibiting
increased Aβ levels and plaque deposition in the brain. Under isoflurane anesthesia we applied
T2-weighted MRI and 1H-MRS using a 4.7T magnet at 3, 8 and 13 months of age in order to
study hippocampal metabolic profile and cerebral volumetric changes over time in female
Tg2576 mice.
Tg2576 mice showed increased amyloid plaque load at the age of 13 months as assessed by
amyloid beta 1-42 immunohistochemistry and ELISA. The plaque load was more robust in
ventral cortex than in hippocampus.
MRS data analysis did not show any statistically significant differences between transgenic (TG)
and wild type (WT) mice in the hippocampal concentrations of NAA, myo-inositol, glutamate,
glutamine, taurine, choline and GABA when studied at 3, 8 and 13 months of age. Volumetric
analysis of total brain, cortex and hippocampus revealed that total brain and cortex were readily
smaller in TG as compared to WT mice already at the age of 3 months. Total brain, cortical and
hippocampal volumes were 7.2, 8.1, and 1.1% smaller in TG than WT mice at 3 months of age.
Interestingly, the difference between TG and WT brain structure volumes increased over age.
The total brain, cortical and hippocampal volumes were 11.2, 14.8 and 12.9 % smaller in TG
than WT mice at 13 months of age.As a conclusion, no significant metabolic differences were
observed in the hippocampus of Tg2576 mice when compared to WT mice, indicating that in the
Tg2576 model the metabolic changes in hippocampus may occur at later age, whereas possibly
earlier in the ventral cortex where the plaque load is more robust already at 13 months of age.
TG mice have smaller brains than WT mice already at 3 months of age, but this difference is
slightly enhanced over time, possibly reflecting increased amyloid beta load related changes.
Disclosures: J.M. Yrjanheikki , None; T. Heikkinen, None; T. Miettinen, None; A. Nurmi,
None; O. Grohn, None; J. Puolivali, None; K. Lehtimaki, None.
Poster
246. Alzheimer's Imaging and Biomarkers II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 246.13/R1
Topic: C.01.o. Imaging and biomarkers
Support: NIH P01 AG09466