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

Research output: Contribution to journalArticle

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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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Vesicular Glutamate Transport Proteins
Vesicular Glutamate Transport Protein 1
Cognition
Dementia
Case-Control Studies
Autopsy
Stroke
Vascular Dementia
Synapses
Amino Acid Transport Systems
Cerebrovascular Disorders
Synaptophysin
Excitatory Amino Acids
Frontal Lobe
Temporal Lobe
Vascular Diseases
Neurotransmitter Agents
Analysis of Variance
Alzheimer Disease
Western Blotting

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

Vesicular glutamate transporter and cognition in stroke : A case-control autopsy study. / Kirvell, S. L.; Elliott, M. S.; Kalaria, R. N.; Hortobágyi, T.; Ballard, C. G.; Francis, P. T.

In: Neurology, Vol. 75, No. 20, 16.11.2010, p. 1803-1809.

Research output: Contribution to journalArticle

Kirvell, SL, Elliott, MS, Kalaria, RN, Hortobágyi, T, Ballard, CG & Francis, PT 2010, 'Vesicular glutamate transporter and cognition in stroke: A case-control autopsy study', Neurology, vol. 75, no. 20, pp. 1803-1809. https://doi.org/10.1212/WNL.0b013e3181fd6328
Kirvell, S. L. ; Elliott, M. S. ; Kalaria, R. N. ; Hortobágyi, T. ; Ballard, C. G. ; Francis, P. T. / Vesicular glutamate transporter and cognition in stroke : A case-control autopsy study. In: Neurology. 2010 ; Vol. 75, No. 20. pp. 1803-1809.
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