Elevation of inactive cleaved annexin A1 in the neocortex is associated with amyloid, inflammatory and apoptotic markers in neurodegenerative dementias
Elevation of inactive cleaved annexin A1 in the neocortex is associated with amyloid, inflammatory and apoptotic markers in neurodegenerative dementias
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DOI：
10.1016/j.neuint.2021.105251
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发表时间：
2022-01-01
影响因子：
4.2
通讯作者：
Lai, Mitchell K. P.
中科院分区：
文献类型：
--
作者：
Chua, Xin Ying;Chong, Joyce R.;Lai, Mitchell K. P.
炎症通常是一个严格调控的过程，其通过包括膜联蛋白A1（AnxA 1）的介质的终止导致炎症反应的消退。在神经退行性痴呆中，慢性神经炎症，沿着聚集的β-淀粉样蛋白（A β）肽的积累和细胞凋亡，长期以来被认为是一种病理标志;但尚不清楚炎症消退的失败是否有助于这种病理生理过程。在这项研究中，我们测量了AnxA 1免疫反应在死后新皮层（布罗德曼区BA 9和BA 40）的特点阿尔茨海默病（AD），帕金森病痴呆（PDD）和路易体痴呆（DLB）患者以及老年对照。在AD和BA 40的DLB中发现无活性切割的AnxA 1升高。在BA 40中，裂解的AnxA 1水平也与淀粉样蛋白生成脑A β、抗炎标志物如IL 10和IL 13以及促凋亡标志物裂解的caspase-3正相关。我们的研究结果表明，在神经退行性痴呆中升高的切割AnxA 1可能反映了患病大脑某些区域炎症消退的失败，并且还支持AnxA 1与淀粉样蛋白病理学，神经炎症和细胞凋亡之间的机制联系。
Inflammation is usually a tightly regulated process whose termination by mediators including Annexin A1 (AnxA1) results in the resolution of inflammatory responses. In neurodegenerative dementias, chronic neuroinflammation, along with accumulation of aggregated beta-amyloid (A beta) peptides and apoptosis, has long been recognized to be a pathological hallmark; but it is unclear whether a failure of inflammation resolution contributes to this pathophysiological process. In this study, we measured AnxA1 immunoreactivities in postmortem neocortex (Brodmann areas BA9 and BA40) of well characterized Alzheimer's disease (AD), Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB) patients as well as aged controls. Inactive cleaved AnxA1 was found to be elevated in AD and DLB in BA40. Levels of cleaved AnxA1 also positively correlated with amyloidogenic brain A beta, anti-inflammatory markers such as IL10 and IL13, as well as with the pro-apoptotic marker cleaved caspase-3 in BA40. Our findings suggest that elevated cleaved AnxA1 in neurodegenerative dementias may reflect a failure of inflammation resolution in certain regions of the diseased brain, and also support a mechanistic link between AnxA1 and amyloid pathology, neuroinflammation and apoptosis.