Non-Aβ component of Alzheimer's disease amyloid (NAC) revisited -: NAC and α-synuclein are not associated with Aβ amyloid
Non-Aβ component of Alzheimer's disease amyloid (NAC) revisited -: NAC and α-synuclein are not associated with Aβ amyloid
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DOI：
10.1016/s0002-9440(10)65220-0
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发表时间：
1999-10-01
影响因子：
6
通讯作者：
Li, QX
中科院分区：
文献类型：
--
作者：
Culvenor, JG;McLean, CA;Li, QX
α-突触核蛋白又称阿尔茨海默病(AD)非Aβ成分淀粉样蛋白(NACP)的前体，是帕金森病(PD)和路易体痴呆(DLB)的主要成分。被称为AD淀粉样非Aβ成分(NAC)的α-SN片段此前已被鉴定为AD淀粉样斑块的组成部分。为了阐明NAC和αSN与Aβ斑块的关系，将抗体提升到αSN的三个区域。所有抗体均能对人脑皮质进行点状标记，对路易小体进行强标记。使用抗αSN(75-91)的抗体标记病理证实的AD病例的皮质和海马区切片，我们在Aβ淀粉样斑块中没有发现NAC的证据。混合DLB/AD患者脑组织切片的双重标记显示，在营养不良的神经突起中存在αSN，其中一些与局限于CA1海马区的Aβ斑块密切相关；在脑匀浆中，经Western分析，αSN主要以16kd的蛋白质形式出现在胞浆中；然而，在DLB和PD病例的SDS不解物的尿素提取物中也发现了大量的聚集和αSN片段。NAC抗体在胞浆和尿素溶解的脑部分中发现了一个6kd的内源性片段，该片段可能是αSN聚集的结果，也可能是加速全长αSN聚集的结果。
alpha-Synuclein (alpha SN), also termed the precursor of the non-A beta component of Alzheimer's disease (AD) amyloid (NACP), is a major component of Lewy bodies and Lewy neurites pathognomonic of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). A fragment of alpha SN termed the non-A beta component of AD amyloid (NAC) had previously been identified as a constituent of AD amyloid plaques. To clarify the relationship of NAC and alpha SN with A beta plaques, antibodies were raised to three domains of alpha SN. All antibodies produced punctate labeling of human cortex and strong labeling of Lewy bodies. Using antibodies to alpha SN(75-91) to label cortical and hippocampal sections of pathologically proven AD cases, we found no evidence for NAC in A beta amyloid plaques. Double labeling of tissue sections in mixed DLB/AD cases revealed alpha SN in dystrophic neuritic processes, some of which were in close association with A beta plaques restricted to the CA1 hippocampal region, In brain homogenates alpha SN was predominantly recovered in the cytosolic fraction as a 16-kd protein on Western analysis; however, significant amounts of aggregated and alpha SN fragments were also found in urea extracts of SDS-insoluble material from DLB and PD cases. NAC antibodies identified an endogenous fragment of 6 kd in the cytosolic and urea-soluble brain fractions, This fragment may be produced as a consequence of alpha SN aggregation or alternatively may accelerate aggregation of the full-length alpha SN.