title: Synaptic protein levels altered in vascular dementia.
abstract: BACKGROUND
  Cerebral ischaemia is the defining pathophysiological abnormality in most forms of vascular dementia (VAD), but the pathogenesis of the dementia remains poorly understood. In Alzheimer's disease (AD), there is early loss of synaptic proteins, but these have been little studied in VAD.
  
  
  METHODS
  We measured synaptophysin, postsynaptic density protein 95 (PSD-95), drebrin, synaptosomal-associated protein 25 (SNAP-25) and vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assays in superior temporal cortex from 11 patients with VAD and, initially, 11 non-dementia controls. We corrected for neuronal content by measurement of neuron-specific enolase. A further 11 controls were subsequently used in a validation study. Simulation of post-mortem delay found that PSD-95 was stable at 4°C but declined slightly at RT. SNAP-25 and drebrin showed good post-mortem stability. Previous studies had shown good post-mortem preservation of synaptophysin and VEGF.
  
  
  RESULTS
  The VAD cases had lower synaptophysin (but P > 0.05 in initial study), significantly lower SNAP-25 (P = 0.024) and significantly higher drebrin (P = 0.020). On comparison with the second control group, the reduction in synaptophysin was significant (P = 0.008), and the other results were confirmed.
  
  
  CONCLUSIONS
  There is probably a reduction in presynaptic proteins in the temporal cortex in VAD, although not as marked as in AD. In VAD, there is also an increase in drebrin, which may be a response to reduced synaptic input.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Lindsey I
authors.initials: LI
authors.lastname: Sinclair
authors.affiliation: School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Tayler
authors.affiliation: School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Seth
authors.initials: S
authors.lastname: Love
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015140:Dementia, Vascular / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D009479:Neuropeptides / Q000032:analysis; D013569:Synapses / Q000378:metabolism*; D016708:Synaptophysin / Q000032:analysis; D050825:Synaptosomal-Associated Protein 25 / Q000032:analysis; D013702:Temporal Lobe / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; C494208:SNAP25 protein, human; C569014:SYP protein, human; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25; D042461:Vascular Endothelial Growth Factor A; C053386:drebrins
keywords: DLG4 protein human; SNAP 25 protein human; apolipoproteins E; drebrins; synaptophysin; vascular dementia