Heinonen O, Soininen H, Sorvari H, Kosunen O, Paljärvi L, Koivisto E, Riekkinen P J
Department of Neurology, University of Kuopio, Finland.
Neuroscience. 1995 Jan;64(2):375-84. doi: 10.1016/0306-4522(94)00422-2.
We studied a synatophysin-like immunoreactivity in the hippocampal formation of patients with definite Alzheimer's disease, multi-infarct dementia, patients with no evidence of clinical dementia with neuropathological findings fulfilling the criteria of possible Alzheimer's disease, and age-matched nondemented controls. Possible Alzheimer's disease cases were of special interest because they were considered to represent early Alzheimer's disease. We also studied the spatial relationship of synaptophysin-like immunopositivity with amyloid-beta-protein immunopositive senile plaques and anti-paired helical filament immunopositive degenerating neurons locally as well as considering the intrinsic circuits in the hippocampal formation. The synaptophysin-like immunoreactivity 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 synapses 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 with multi-infarct dementia suggests that the loss of synapses is centrally involved in the pathogenesis of Alzheimer's disease and not dementia per se. There was no spatial correlation between loss of synapses and amyloid-beta-protein positive senile plaques. Moreover, we could not find a strict spatial relationship between senile plaques and degenerating neurons. Our results do not support the amyloid cascade hypothesis of Alzheimer's disease that local accumulation of amyloid-beta-protein leads to the loss of synapses.
我们研究了确诊为阿尔茨海默病、多发性梗死性痴呆患者，无临床痴呆证据但神经病理学发现符合可能阿尔茨海默病标准的患者，以及年龄匹配的非痴呆对照者海马结构中突触素样免疫反应性。可能的阿尔茨海默病病例特别受关注，因为它们被认为代表早期阿尔茨海默病。我们还研究了突触素样免疫阳性与淀粉样β蛋白免疫阳性老年斑以及抗双螺旋丝免疫阳性变性神经元在局部的空间关系，同时也考虑了海马结构中的内在神经回路。与对照组相比，确诊和可能患有阿尔茨海默病的患者海马和内嗅皮质中的突触素样免疫反应性降低，但多发性梗死性痴呆患者未出现这种情况。可能和确诊的阿尔茨海默病患者突触同等程度的丧失支持了突触丧失是阿尔茨海默病早期现象的假说。多发性梗死性痴呆患者突触素样免疫反应性未改变，这表明突触丧失主要参与阿尔茨海默病的发病机制，而非痴呆本身。突触丧失与淀粉样β蛋白阳性老年斑之间不存在空间相关性。此外，我们未发现老年斑与变性神经元之间存在严格的空间关系。我们的结果不支持阿尔茨海默病的淀粉样蛋白级联假说，即淀粉样β蛋白的局部积累导致突触丧失。
