Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains.
Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains.
复制标题
DOI：
10.1186/alzrt121
复制
发表时间：
2012-05-23
期刊：
影响因子：
--
通讯作者：
Golde TE
中科院分区：
文献类型：
--
作者：
Moore BD;Chakrabarty P;Levites Y;Kukar TL;Baine AM;Moroni T;Ladd TB;Das P;Dickson DW;Golde TE
阿尔茨海默病（AD）的一个标志是存在由聚集的β淀粉样蛋白（Aβ）肽组成的老年斑。病理性衰老（PA）是一种死后分类，用于描述脑供者死前没有伴随认知能力下降史，且斑块病理程度与阿尔茨海默病相似的大脑，皮质tau蛋白病理极少。PA可能代表AD的前驱期，a β积累的良性形式，或固有的个体抵抗a β积累的毒性作用。为了尝试区分这些可能性，我们系统地表征了PA， AD和非痴呆对照（NDC）脑死后的一系列a β肽。采用tris缓冲盐水（TBS）、放射免疫沉淀缓冲液（RIPA）、2%十二烷基硫酸钠（SDS）和70%甲酸（FA）分别从16例AD、8例PA和6例NDC患者的前额叶皮层提取Aβ。采用1)a β夹心elisa， 2)免疫沉淀-质谱（IP/MS）和3)免疫印迹法对这些提取物进行分析。这些研究使我们能够评估Aβ水平和溶解度，肽谱和低聚物组装。在几乎所有提取物（TBS、RIPA、2% SDS和70% FA）中，Aβ1-40、Aβ1-42、Aβ总和Aβx-42的平均水平在AD中最高。平均而言，PA的水平略低，个体PA和AD病例的Aβ水平之间存在广泛的重叠。利用IP/MS技术检测到的Aβ肽谱也显示了PA和AD脑提取物之间广泛的相似性。在选定的AD脑提取物中，与PA患者相比，我们检测到更多的氨基末端截断的a β肽，但这些肽只占观察到的a β的一小部分。western blotting结果显示，PA组和AD组的Aβ组装没有一致的差异。我们发现PA和AD大脑中Aβ水平、肽谱、溶解度和sds稳定的寡聚物组装之间存在广泛的重叠，只有细微的定量差异。这些横截面数据表明，PA和AD中Aβ的积累非常相似。这些数据将与PA代表AD的前驱阶段或对a β毒性作用的抗性相一致。
A hallmark of Alzheimer's disease (AD) is the presence of senile plaques composed of aggregated amyloid β (Aβ) peptides. Pathological aging (PA) is a postmortem classification that has been used to describe brains with plaque pathology similar in extent to AD, minimal cortical tau pathology, and no accompanying history of cognitive decline in the brain donor prior to death. PA may represent either a prodromal phase of AD, a benign form of Aβ accumulation, or inherent individual resistance to the toxic effects of Aβ accumulation. To attempt to distinguish between these possibilities we have systematically characterized Aβ peptides in a postmortem series of PA, AD and non-demented control (NDC) brains. Aβ was sequentially extracted with tris buffered saline (TBS), radioimmunoprecipitation buffer (RIPA), 2% sodium dodecyl sulfate (SDS) and 70% formic acid (FA) from the pre-frontal cortex of 16 AD, eight PA, and six NDC patients. These extracts were analyzed by 1) a panel of Aβ sandwich ELISAs, 2) immunoprecipitation followed by mass spectrometry (IP/MS) and 3) western blotting. These studies enabled us to asses Aβ levels and solubility, peptide profiles and oligomeric assemblies. In almost all extracts (TBS, RIPA, 2% SDS and 70% FA) the average levels of Aβ1-40, Aβ1-42, Aβ total, and Aβx-42 were greatest in AD. On average, levels were slightly lower in PA, and there was extensive overlap between Aβ levels in individual PA and AD cases. The profiles of Aβ peptides detected using IP/MS techniques also showed extensive similarity between the PA and AD brain extracts. In select AD brain extracts, we detected more amino-terminally truncated Aβ peptides compared to PA patients, but these peptides represented a minor portion of the Aβ observed. No consistent differences in the Aβ assemblies were observed by western blotting in the PA and AD groups. We found extensive overlap with only subtle quantitative differences between Aβ levels, peptide profiles, solubility, and SDS-stable oligomeric assemblies in the PA and AD brains. These cross-sectional data indicate that Aβ accumulation in PA and AD is remarkably similar. Such data would be consistent with PA representing a prodromal stage of AD or a resistance to the toxic effects of Aβ.
登录
查看更多内容
DOI：
10.1006/bbrc.2000.3490
发表时间：
2000-09-24
影响因子：
3.1
作者：
Harigaya, Y;Saido, TC;Younkin, SG
通讯作者：
Younkin, SG
影响因子：
2.9
作者：
He, WL;Barrow, CJ
通讯作者：
Barrow, CJ
影响因子：
16.2
作者：
Ashe, Karen H.;Zahs, Kathleen R.
通讯作者：
Zahs, Kathleen R.
影响因子：
4.8
作者：
Boutte, Angela M.;Woltjer, Randall L.;Montine, Thomas J.
通讯作者：
Montine, Thomas J.
影响因子：
4.8
作者：
Jawhar, Sadim;Wirths, Oliver;Bayer, Thomas A.
通讯作者：
Bayer, Thomas A.