LOSS OF SYNAPTOPHYSIN-LIKE IMMUNOREACTIVITY IN THE HIPPOCAMPAL-FORMATION IS AN EARLY PHENOMENON IN ALZHEIMERS-DISEASE

We studied a synaptophysin-like immunoreactivity in the hippocampal fo rmation of patients with definite Alzheimer's disease, multi-infarct d ementia, patients with no evidence of clinical dementia with neuropath ological findings fulfilling the criteria of possible Alzheimer's dise ase, and age-matched nondemented controls. Possible Alzheimer's diseas e cases were of special interest because they were considered to repre sent early Alzheimer's disease. We also studied the spatial relationsh ip of synaptophysin-like immunopositivity with amyloid-beta-protein im munopositive senile plaques and anti-paired helical filament immunopos itive degenerating neurons locally as well as considering the intrinsi c circuits in the hippocampal formation. The synaptophysin-like immuno reactivity was decreased in the hippocampus and the entorhinal cortex in patients with definite and possible Alzheimer's disease but not in multi-infarct dementia patients compared to controls. Equal loss of sy napses in possible and definite Alzheimer's disease patients supports the hypothesis that synaptic loss is an early phenomenon in Alzheimer' s disease. Unchanged synaptophysin-like immunopositivity in patients w ith multi-infarct dementia suggests that the loss of synapses is centr ally involved in the pathogenesis of Alzheimer's disease and not demen tia per se. There was no spatial correlation between loss of synapses and amyloid-beta-protein positive senile plaques. Moreover, we could n ot find a strict spatial relationship between senile plaques and degen erating neurons. Our results do not support the amyloid cascade hypoth esis of Alzheimer's disease that local accumulation of amyloid beta-pr otein leads to the loss of synapses.