Psychosis in Alzheimer disease: postmortem magnetic resonance spectroscopy evidence of excess neuronal and membrane phospholipid pathology.
Psychosis in Alzheimer disease: postmortem magnetic resonance spectroscopy evidence of excess neuronal and membrane phospholipid pathology.
复制标题
阿尔茨海默病中的精神病：死后磁共振波谱学证据表明神经元和膜磷脂病理学过多。
DOI：
10.1016/s0197-4580(02)00009-x
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发表时间：
2002
影响因子：
4.2
通讯作者：
Klunk,WilliamE
中科院分区：
文献类型：
--
作者：
Sweet,RobertA;Panchalingam,Kanagasabai;Pettegrew,JayW;McClure,RichardJ;Hamilton,RonaldL;Lopez,OscarL;Kaufer,DanielI;DeKosky,StevenT;Klunk,WilliamE
背景阿尔茨海默病（AD+psychosis，AD+P）患者的精神病性症状的存在是一种以更严重的认知障碍和更迅速恶化的病程为特征的表型的标志。虽然AD+P与更严重的神经病理学不一致，但没有先前的研究检查了神经元和突触完整性的测量。目的确定AD+P是否与神经元和突触完整性破坏的证据有关，如N-乙酰基-L-天冬氨酸和膜分解产物的磁共振波谱（MRS）测量所示，方法采用31 P和1H MRS对有和无精神病性症状史的AD患者的脑组织进行了高氯酸提取物的研究。所有受试者的特点是存在共病皮质路易体病理和精神抑制剂的使用史。对所有受试者的背外侧前额叶、上级颞叶、顶叶下部和枕叶皮质、杏仁核和小脑的脑组织进行了检查。统计分析占整个大脑区域内subjects.ResultsAD+P科目的相关观察表现出显着的升高glycerophosphohoethanolamine和显着减少N-乙酰基-L-天冬氨酸。组间差异是最大的新皮层脑regions. ConclusionExcessive损伤的新皮层神经元和突触的完整性可能提供的基础AD+ P的结构基板。确认这些研究结果使用在体内MRS措施表明。
BackgroundThe presence of psychotic symptoms in Alzheimer Disease subjects (AD+psychosis, AD+P) is a marker for a phenotype characterized by more severe cognitive impairment and a more rapidly deteriorating course. Although AD+P has been inconsistently associated with more severe neuropathology, no prior studies have examined measures of neuronal and synaptic integrity.ObjectiveTo determine whether AD+P is associated with evidence of disrupted neuronal and synaptic integrity, as indicated by magnetic resonance spectroscopy (MRS) measurement of N-acetyl-l-aspartate and the membrane breakdown products, glycerophosphocholine and glycerophosphoethanolamine.Methods31P and1H MRS studies of perchloric acid extract from postmortem brain of AD subjects with and without a history of psychotic symptoms. All subjects were characterized for the presence of comorbid cortical Lewy body pathology and for history of neuroleptic use. Brain tissue from dorsolateral prefrontal, superior temporal, inferior parietal, and occipital cortex, amygdala, and cerebellum were examined in all subjects. Statistical analysis accounted for correlated observations across brain regions within-subjects.ResultsAD+P subjects demonstrated significant elevations of glycerophosphoethanolamine and significant reductions of N-acetyl-l-aspartate. Between group differences were greatest in neocortical brain regions.ConclusionExcess impairment of neocortical neuronal and synaptic integrity may provide the structural substrate underlying AD+P. Confirmation of these findings using in vivo MRS measures is indicated.