Abstract
IntroductionCerebral 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.Materials and MethodsWe 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.ResultsThe 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.ConclusionThere 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.
Highlights
Cerebral ischaemia is the defining pathophysiological abnormality in most forms of vascular dementia (VAD), but the pathogenesis of the dementia remains poorly understood
synaptosomal-associated protein 25 (SNAP-25), PSD-95 and drebrin have not previously been studied in VAD. We have addressed this by measuring concentrations of synaptophysin, SNAP-25, PSD-95 and drebrin in post-mortem superior temporal cortex from patients with VAD and nondemented controls
The post-mortem delay was significantly greater for the VAD cases (P = 0.007)
Summary
Cerebral ischaemia is the defining pathophysiological abnormality in most forms of vascular dementia (VAD), but the pathogenesis of the dementia remains poorly understood. In VAD, there is an increase in drebrin, which may be a response to reduced synaptic input It is a major cause of cognitive decline, with an age-adjusted incidence estimated at 11–13 per 1000 per year [1,2,3], vascular dementia (VAD) has been studied biochemically to a much lesser extent than have other types of dementia. This is partly because it has proven difficult to define in research terms [4,5]. There is evidence that reduced cerebral blood flow may contribute to the progression of AD [11,12,13,14,15] and that the
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