SYNAPSE LOSS IN FRONTAL-CORTEX BIOPSIES IN ALZHEIMERS-DISEASE - CORRELATION WITH COGNITIVE SEVERITY
SYNAPSE LOSS IN FRONTAL-CORTEX BIOPSIES IN ALZHEIMERS-DISEASE - CORRELATION WITH COGNITIVE SEVERITY
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DOI：
10.1002/ana.410270502
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发表时间：
1990-05-01
影响因子：
11.2
通讯作者：
SCHEFF, SW
中科院分区：
文献类型：
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作者：
DEKOSKY, ST;SCHEFF, SW
对8例轻中度阿尔茨海默病(AD)患者右侧额叶皮质组织的超微结构研究表明，与年龄匹配的对照组(n=9，死后13小时)相比，S病(AD)患者大脑Brodmann区9区III层的突触数目明显减少。在年龄匹配的AD尸检标本中，突触数量进一步下降。AD患者脑内突触平均长度明显增大，与突触丢失程度相关；随着突触密度的降低，突触大小增大。突触的扩大，加上突触数量的减少，使得接受活组织检查的患者单位体积的突触接触总面积保持稳定。在AD患者尸检中，平均突触接触面积没有进一步扩大。在接受活组织检查的患者中，突触计数和简易智力状态检查的分数之间存在显著的相关性。精神状态得分越低，突触丢失的程度越大。胆碱乙酰转移酶活性在活检组显著降低，在AD尸检标本中进一步降低。胆碱乙酰转移酶活性与简易智能状态检查评分和突触数目之间无相关性。有证据表明AD神经束具有神经可塑性；接受活组织检查的患者突触接触面积增加，并可能补偿突触数量的丢失。但在疾病末期，大脑皮质的代偿能力被超过，突触数量和突触接触面积都下降了。以突触丧失为指标的神经元连接丧失，可以预测接受活组织检查的患者的认知障碍程度，并表明AD大脑的结构变化在一定程度上不太可能受到药物治疗的影响。
Ultrastructural studies of biopsied cortical tissue from the right frontal lobe of 8 patients with mild to moderate Alzheimer''s disease (AD) revealed that the number of synapses in lamina III of Brodmann''s area 9 was significantly decreased when compared with the number in age-matched control brains (n = 9; postmortem time, < 13 hours). Further decline in synaptic number was seen in age-matched autopsied AD specimens. In the AD brains there was significant enlargement of the mean apposition length, which correlated with degree of synapse loss; as synapse density declined, synapse size increased. The enlargement of synapses, coupled with the decrease in synaptic number, allowed the total synaptic contact area per unit volume to remain stable in the patients who underwent biopsy. In autopsied subjects who had AD, there was no further enlargement of mean synaptic contact area. There was a significant correlation between synapse counts and scores on the Mini-Mental State examination in the patients who underwent biopsy. Lower mental status scores were associated with greater loss of synapses. Choline acetyltransferase activity was significantly decreased in the biopsied group and declined further in the autopsied specimens of AD. There was no relationship between choline acetyltransferase activity and scores on the Mini-Mental State examination or synapse number. There is evidence of neural plasticity in the AD neuropil; synaptic contact size increased in patients who had biopsy and possibly compensated for the numerical loss of synapses. But by end stage of the disease, the ability of the cortex to compensate was exceeded and both synapse number and synaptic contact area declined. The loss of neuronal connectivity, indexed by loss of synapses, predicted the degree of cognitive impairment in the patients who underwent biopsy and indicated a degree of structural change in AD brain not likely to be affected by pharmacotherapy.