Age-related metabolic changes in the hippocampus of APP(Swe)/PS1(dE9) mice were measured with long echo-time in vivo H-1-magnetic resonance spectroscopy (H-1-MRS). Thioflavine S staining and Nissl staining were used to characterize deposition of Ab aggregates and neuronal degeneration in the transgenic animals, respectively. The results showed that the APP(Swe)/PS1(dE9) mice had significantly decreased hippocampal N-acetyl aspartate (NAA)/total creatine (tCr) level at 16 months of age, which was associated with degeneration of and intracellular deposition of thioflavine S-positive materials in hippocampal CA3 pyramidal neurons. The results of this study provide direct evidence showing association among Ab pathology (intracellular deposition of thioflavine S-positive materials), neuronal degeneration, and metabolic changes observable with in vivo H-1-MRS in the hippocampus of APP(Swe)/PS1(dE9) mice. (c) 2010 Wiley-Liss, Inc.