Molecular subtypes of Alzheimer's disease.
Molecular subtypes of Alzheimer's disease.
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DOI：
10.1038/s41598-018-21641-1
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发表时间：
2018-02-19
影响因子：
4.6
通讯作者：
Tagliavini F
中科院分区：
文献类型：
--
作者：
Di Fede G;Catania M;Maderna E;Ghidoni R;Benussi L;Tonoli E;Giaccone G;Moda F;Paterlini A;Campagnani I;Sorrentino S;Colombo L;Kubis A;Bistaffa E;Ghetti B;Tagliavini F
蛋白质错误折叠和聚集是包括阿尔茨海默病（AD）在内的几种神经退行性疾病的核心特征，其中β淀粉样蛋白（a β）肽的组装以实质和/或血管淀粉样蛋白的形式积聚在大脑中。一个被广泛接受的概念是，阿尔茨海默病具有不同的临床和神经病理表型。最近的研究表明，Aβ组装可能在AD大脑中具有结构差异，并且这种多形性组装可能与不同的疾病表型相关。我们发现，在散发性和遗传性AD中，淀粉样蛋白聚集体在Aβ物种的生化组成上有所不同。这些差异影响了Aβ组装体的物理化学性质，包括聚集动力学、蛋白酶降解抗性和播种能力。接种含有聚集性Aβ的脑提取物可在动物模型中诱导和繁殖Aβ-淀粉样变性。我们发现，当注射到小鼠体内时，来自AD患者的具有不同Aβ分子谱的脑匀浆能够诱导不同模式的Aβ-淀粉样变性。总的来说，这些数据表明，Aβ肽的混合物组装成不同的Aβ种子导致淀粉样蛋白不同亚型的形成，这些淀粉样蛋白具有不同的物理化学和生物学特性，从而导致不同AD分子亚群的产生。
Protein misfolding and aggregation is a central feature of several neurodegenerative disorders including Alzheimer’s disease (AD), in which assemblies of amyloid β (Aβ) peptides accumulate in the brain in the form of parenchymal and/or vascular amyloid. A widely accepted concept is that AD is characterized by distinct clinical and neuropathological phenotypes. Recent studies revealed that Aβ assemblies might have structural differences among AD brains and that such pleomorphic assemblies can correlate with distinct disease phenotypes. We found that in both sporadic and inherited forms of AD, amyloid aggregates differ in the biochemical composition of Aβ species. These differences affect the physicochemical properties of Aβ assemblies including aggregation kinetics, resistance to degradation by proteases and seeding ability. Aβ-amyloidosis can be induced and propagated in animal models by inoculation of brain extracts containing aggregated Aβ. We found that brain homogenates from AD patients with different molecular profiles of Aβ are able to induce distinct patterns of Aβ-amyloidosis when injected into mice. Overall these data suggest that the assembly of mixtures of Aβ peptides into different Aβ seeds leads to the formation of distinct subtypes of amyloid having distinctive physicochemical and biological properties which result in the generation of distinct AD molecular subgroups.
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影响因子：
12.7
作者：
Janocko NJ;Brodersen KA;Soto-Ortolaza AI;Ross OA;Liesinger AM;Duara R;Graff-Radford NR;Dickson DW;Murray ME
通讯作者：
Murray ME
DOI：
10.1523/jneurosci.3088-11.2011
发表时间：
2011-10-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Langer F;Eisele YS;Fritschi SK;Staufenbiel M;Walker LC;Jucker M
通讯作者：
Jucker M
影响因子：
6
作者：
Bolmont, Tristan;Clavaguera, Florence;Jucker, Mathias
通讯作者：
Jucker, Mathias
影响因子：
4.2
作者：
Hellström-Lindahl E;Viitanen M;Marutle A
通讯作者：
Marutle A
影响因子：
2.3
作者：
Cohen, Mark;Appleby, Brian;Safar, Jiri G.
通讯作者：
Safar, Jiri G.