Reduction of hippocampal N-acetyl aspartate level in aged APP(Swe)/PS1(dE9) transgenic mice is associated with degeneration of CA3 pyramidal neurons.
Age-related metabolic changes in the hippocampus of APP(Swe)/PS1(dE9) mice were measured with long echo-time in vivo (1)H-magnetic resonance spectroscopy ((1)H-MRS). Thioflavine S staining and Nissl staining were used to characterize deposition of Aβ 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 Aβ pathology (intracellular deposition of thioflavine S-positive materials), neuronal degeneration, and metabolic changes observable with in vivo (1)H-MRS in the hippocampus of APP(Swe)/PS1(dE9) mice.
Xu
Wei
W
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, China.
Zhan
Yanqiang
Y
Huang
Wei
W
Wang
Xuxia
X
Zhang
Sumin
S
Lei
Hao
H
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D052160:Benzothiazoles; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology; D003401:Creatine / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013844:Thiazoles
D016564:Amyloid beta-Protein Precursor; D052160:Benzothiazoles; C508853:PSEN1 protein, human; D053764:Presenilin-1; D013844:Thiazoles; C009462:thioflavin T; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine