Quantitative assessment of the synaptophysin immuno-reactivity of the cortical neuropil in various neurodegenerative disorders with dementia.
It has remained a matter of debate until now whether amyloid and tangle pathology may be regarded as the main causes of the dementia in Alzheimer'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 17 cases of AD, 1 case with a 10-month episode of dementia and cortical amyloid deposition, 5 cases of Huntington's disease (HD) with dementia, 11 cases of parkinsonism (PD), 5 with dementia (PD-D) and 16 controls. The immunoreactivity was assessed in two layers (molecular, pyramidal) of three regions (frontal, occipital, hippocampus) by means of automated black-and-white image analysis. In AD we found a rather diffuse reduction of the cortical synaptophysin expression of up to 26.5% (mean 11%) of the controls. No correlation was found between synaptophysin expressivity and age either in AD or in the controls. Univariate analyses revealed only a very weak negative correlation between the density of beta A4-immunoreactive cortical plaques and the intensity of the synaptophysin staining, while in a multivariate analysis the plaque density did not show any impact on the latter. In HD a reduction of the synaptophysin immunoreactivity of the cortical neuropil was also found (mean 10.4%), with 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.
Zhan
S S
SS
Institute of Neuropathology, University of Heidelberg, FRG.
Beyreuther
K
K
Schmitt
H P
HP
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000276:immunology / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000378:metabolism*; D016612:Paraffin Embedding; D010300:Parkinson Disease / Q000378:metabolism; D016708:Synaptophysin / Q000276:immunology / Q000378:metabolism*
D000682:Amyloid; D016708:Synaptophysin