QUANTITATIVE ASSESSMENT OF THE SYNAPTOPHYSIN IMMUNO-REACTIVITY OF THECORTICAL NEUROPIL IN VARIOUS NEURODEGENERATIVE DISORDERS WITH DEMENTIA

It has remained a matter of debate until now whether amyloid and tangl e pathology may be regarded as the main causes of the dementia in Alzh eimer's disease (AD) or only as markers of the disease. In the present study we examined the synaptophysin immunoreactivity of the cortical neuropil as a measure of its synapse density, in 1 7 cases of AD, 1 ca se with a 10-month episode of dementia and cortical amyloid deposition , 5 cases of Huntington's disease (HD) with dementia, 11 cases of park insonism (PD), 5 with dementia (PD-D) and 16 controls. The immunoreact ivity was assessed in two layers (molecular, pyramidal) of three regio ns (frontal, occipital, hippocampus) by means of automated black-and-w hite image analysis. In AD we found a rather diffuse reduction of the cortical synaptophysin expression of up to 26.5% (mean 11%) of the con trols. No correlation was found between synaptophysin expressivity and age either in AD or in the controls. Univariate analyses revealed onl y a very weak negative correlation between the density of betaA4-immun oreactive cortical plaques and the intensity of the synaptophysin stai ning, while in a multivariate analysis the plaque density did not show any impact on the latter. In HD a reduction of the synaptophysin immu noreactivity of the cortical neuropil was also found (mean 10.4%), wit h a predominance in the pyramidal layer of the neocortex. The same was true for PD (5.3%) and PD-D (8.2%). Our results support the view that loss of synapses in the cortical neuropil may be a significant factor for the development of organic dementia, while the amyloid pathology in AD is more likely a marker of the disease.