Synaptophysin Immunoreactivity of the Cortical Neuropil in Vascular Dementia of Binswanger Type Compared with the Dementia of Alzheimer Type and Nondemented Controls

Abstract

It has been shown recently that in Alzheimer''s disease the degree of dementia is strongly correlated with a reduction of the synaptophysin reactivity of the cortical neuropil as a measure of synapse density, while counts of neuritic plaques showed a weak correlation. This suggests that mechanisms acting at the synaptic level, finally resulting in a numerical decline of synapses, may represent an important factor in the pathogenesis of dementia. Under these aspects, we wanted to examine whether changes of synaptophysin immunoreactivity may also occur in dementia of vascular origin such as Binswanger''s disease, where the white matter atrophy is usually conceived to be the main morphologic correlate of dementia. However, infrequently patients with morphologically typical Binswanger''s subcortical encephalopathy including white matter atrophy are not demented. We found in 9 cases of vascular dementia of Binswanger type a significant reduction in synaptophysin immunoreactivity of the cortical neuropil (9.1 %), the magnitude of which was not much less than in Alzheimer type dementia (10.9 %). These results suggest that a reduction in cortical synaptic population density may also play a significant role in the pathogenesis of dementia in Binswanger''s disease. In view of the fact that similar conditions have been shown to occur in neurodegenerative disorders with dementia other than Alzheimer type dementia, there seems to be evidence for a possible common pathogenetic link between these forms of dementia at the synaptic level, where different etiologic factors may result in similar changes.

Decrease in Cortical Benzodiazepine Receptors in Symptomatic Patients With Leukoaraiosis

“…10 Indeed, loss of synaptophysin, a neuronal marker, in the cerebral cortex has been reported in the brains of BD patients. 34 Our results are consistent with these findings and further suggest that neuronal injury in the cerebral cortex occurs in BD patients.…”

Neuropathology of Vascular Cognitive Impairment and Vascular Dementia

“…There are no good studies of neuronal populations in the cerebral cortex, despite the finding that diffuse cerebral atrophy is a good radiological correlate of VCI in addition t o focal lesions. A single study of cortical synaptic density in Binswanger's disease showed equivalent loss to that found in Alzheimer's disease (Zhan et al, 1994). There is similar evidence for diffuse changes in neurochemical parameters summarized in the paper by Court and Perry in this supplement.…”

Understanding the pathology of vascular cognitive impairment

“…Frontal impairment in VaD is responsible for greater executive dysfunction in comparison with AD patients who show more severe impairment of attentional shifting and working memory [39]. Synaptophysin immunoreactivity as a measure of synapse protein density in the cortex is severely reduced in Binswanger's disease [40]. Preclinical [41] and clinical evidence [42] indicate that cholinergic deficit, similar to that seen in AD, may be associated with VaD, suggesting that these patients may benefit from treatment with cholineresterase inhibitors, which has been confirmed by recent studies [43,44].…”