title: Vesicular glutamate transporter and cognition in stroke: a case-control autopsy study.
abstract: OBJECTIVE
  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.
authors.affiliation: King's College London, Wolfson Centre for Age-Related Diseases, London, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Kirvell
authors.forename: M S
authors.initials: MS
authors.lastname: Elliott
authors.forename: R N
authors.initials: RN
authors.lastname: Kalaria
authors.forename: T
authors.initials: T
authors.lastname: Hortobágyi
authors.forename: C G
authors.initials: CG
authors.lastname: Ballard
authors.forename: P T
authors.initials: PT
authors.lastname: Francis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D015140:Dementia, Vascular / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology; D020521:Stroke / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D050598:Vesicular Glutamate Transport Protein 1 / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C493464:SLC17A7 protein, human; D050598:Vesicular Glutamate Transport Protein 1