Down-regulation of vesicular glutamate transporters precedes cell loss and pathology in Alzheimer's disease
Article first published online: 5 JUL 2006
Journal of Neurochemistry
Volume 98, Issue 3, pages 939–950, August 2006
How to Cite
Kirvell, S. L., Esiri, M. and Francis, P. T. (2006), Down-regulation of vesicular glutamate transporters precedes cell loss and pathology in Alzheimer's disease. Journal of Neurochemistry, 98: 939–950. doi: 10.1111/j.1471-4159.2006.03935.x
- Issue published online: 5 JUL 2006
- Article first published online: 5 JUL 2006
- Received January 23, 2006; revised manuscript received March 29, 2006; accepted March 29, 2006.
Vol. 100, Issue 6, 1713, Article first published online: 23 JAN 2007
- Alzheimer's disease;
- vesicular transporter
Alzheimer's disease (AD) is characterized pathologically by plaques, tangles, and cell and synapse loss. As glutamate is the principle excitatory neurotransmitter of the CNS, the glutamatergic system may play an important role in AD. An essential step in glutamate neurotransmission is the concentration of glutamate into synaptic vesicles before release from the presynaptic terminal. Recently a group of proteins responsible for uptake has been identified – the vesicular glutamate transporters (VGLUTs). The generation of antibodies has facilitated the study of glutamatergic neurones. Here, we used antibodies to the VGLUTs together with immunohistochemistry and western blotting to investigate the status of glutamatergic neurones in temporal, parietal and occipital cortices of patients with AD; these regions were chosen to represent severely, moderately and mildly affected regions at the end stage of the disease. There was no change in expression of the synaptic markers in relation to total protein in the temporal cortex, but a significant reduction in synaptophysin and VGLUT1 was found in both the parietal and occipital cortices. These changes were found to relate to the number of tangles in the temporal cortex. There were no correlations with either mental test score or behaviour syndromes, with the exception of depression.