Altered neurochemical profile in the McGill-R-Thy1-APP rat model of Alzheimer's disease: a longitudinal in vivo 1H MRS study

• Published in: Journal of neurochemistry 2012-11, Vol.123 (4), p.532-541
• Main Authors: Nilsen, Linn H., Melø, Torun M., Sæther, Oddbjørn, Witter, Menno P., Sonnewald, Ursula
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Alzheimer's disease; Biological and medical sciences; biomarkers; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; GABA; glutamate; Indexing in process; Medical sciences; metabolism; Metabolites; N-acetylaspartate; Neurochemistry; Neurology; Organic mental disorders. Neuropsychology; Pathology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; transgenic rats
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.12003

We investigated metabolite levels during the progression of pathology in McGill‐R‐Thy1‐APP rats, a transgenic animal model of Alzheimer's disease, and in healthy age‐matched controls. Rats were subjected to in vivo 1H magnetic resonance spectroscopy (MRS) of the dorsal hippocampus at age 3, 9 and 12 months and of frontal cortex at 9 and 12 months. At 3 months, a stage in which only Aβ oligomers are present, lower glutamate, myo‐inositol and total choline content were apparent in McGill‐R‐Thy1‐APP rats. At age 9 months, lower levels of glutamate, GABA, N‐acetylaspartate and total choline and elevated myo‐inositol and taurine were found in dorsal hippocampus, whereas lower levels of glutamate, GABA, glutamine and N‐acetylaspartate were found in frontal cortex. At age 12 months, only the taurine level was significantly different in dorsal hippocampus, whereas taurine, myo‐inositol, N‐acetylaspartate and total creatine levels were significantly higher in frontal cortex. McGill‐R‐Thy1‐APP rats did not show the same changes in metabolite levels with age as displayed in the controls, and overall, prominent and complex metabolite differences were evident in this transgenic rat model of Alzheimer's disease. The findings also demonstrate that in vivo 1H MRS is a powerful tool to investigate disease‐related metabolite changes in the brain. The study of transgenic animals is instrumental to achieve a better understanding of early aspects of Alzheimer's disease. We found prominent metabolite alterations at the pre‐plaque stage of 3 months and also during the progression of AD pathology in McGill‐R‐Thy1‐APP rats. The findings demonstrate that in vivo 1H MRS is a powerful tool to investigate disease‐related metabolite changes in brain.