Affiliations: [a] Department of Neurology, Department of Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud university medical center, Nijmegen, The Netherlands | [b] Department of Nuclear Medicine and PET Research, VU University Medical Centre, Amsterdam, The Netherlands | [c] Department of Laboratory Medicine, Laboratory of Genetic, Endocrine and Metabolic Diseases, Radboud university medical center, Nijmegen, The Netherlands
Correspondence:
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Correspondence to: Marcel M. Verbeek, Department of Neurology, 830 LGEM, Radboud university medical center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Tel.: +31 243615192; Fax: +31 243668754; E-mail: [email protected].
Abstract: Amyloid-β (Aβ) deposition, one of the main hallmarks of Alzheimer's disease (AD), has been linked to glutamatergic dysfunction, i.e., increased stimulation of synaptic glutamate receptors that may ultimately result in neuronal loss. It was our aim to study the effect of Aβ on multiple components of the glutamatergic system, and therefore we assessed the expression of several glutamate-related proteins and amino acids in the TgSwDI mouse model for Aβ pathology. We determined that in TgSwDI mice, levels of several amino acids are altered, in particular that of glycine. Protein changes were only found in 9-month-old TgSwDI mice with extensive Aβ deposits, with the most prominent change an increased expression of vesicular glutamate transporter 1 (vGlut1). Autoradiography experiments demonstrated that, while the number of activated N-methyl-D-aspartic acid (NMDA) receptors was unchanged in TgSwDI mice, binding of the NMDA receptor radioligand [3H]MDL-105,519 to the glycine-binding site of these receptors was increased. Although there are some discrepancies between our results and those found in AD patients, our results suggest that several components of the glutamatergic system might serve as meaningful markers to monitor the progression of AD.
Keywords: Alzheimer's disease, amino acid analysis, autoradiography, amyloid-β, glutamate, glycine, TgSwDI mice, vesicular glutamate transporter 1, western blot
