Vesicular glutamate transporter and cognition in stroke: A case-control autopsy study

S. L. Kirvell, M. S. Elliott, R. N. Kalaria, T. Hortobágyi, C. G. Ballard, P. T. Francis

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Abstract

Objectives: Vascular dementia (VaD) accounts for approximately 15%-20% of all dementias, but the relationship of progressive cognitive impairment to neurochemical changes is poorly understood. We have therefore investigated glutamatergic synaptic markers in VaD. Methods: We used homogenates prepared from gray matter from 2 neocortical regions (Brodmann area [BA] 9 and BA 20) and Western blotting to determine the concentrations of key components of the glutamatergic neurotransmitter system, vesicular glutamate transporter 1 (VGLUT1) and excitatory amino acid transporter EAAT2 (GLT-1), and the ubiquitous synaptic protein, synaptophysin, in 73 individuals-48 patients with cerebrovascular disease with and without dementia, 10 patients with AD, and 15 controls-in a case-control design. Results: VGLUT1 concentrations in BA 20 and BA 9 were correlated with CAMCOG total (Rs 0.525, p = 0.018, n = 20; Rs 0.560, p = 0.002, n = 27) and CAMCOG memory scores (Rs 0.616, p = 0.004, n = 20; Rs 0.675, p = 0.000, n = 27). VGLUT1 concentration in BA 9 differed between the different dementia groups and the stroke no dementia group (1-way analysis of variance F = 6.69, p = 0.001 and Bonferroni p < 0.01 in each case), with subjects with stroke who did not develop dementia exhibiting the highest mean value for VGLUT1. Conclusions: These data suggest that loss of glutamatergic synapses is a feature of VaD and Alzheimer disease but the preservation of synapses, in particular glutamatergic synapses, in the frontal cortex against the temporal cortex plays a role in sustaining cognition and protecting against dementia following a stroke.

Original languageEnglish
Pages (from-to)1803-1809
Number of pages7
JournalNeurology
Volume75
Issue number20
DOIs
Publication statusPublished - nov. 16 2010

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ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Kirvell, S. L., Elliott, M. S., Kalaria, R. N., Hortobágyi, T., Ballard, C. G., & Francis, P. T. (2010). Vesicular glutamate transporter and cognition in stroke: A case-control autopsy study. Neurology, 75(20), 1803-1809. https://doi.org/10.1212/WNL.0b013e3181fd6328