The mechanistic link between selective vulnerability of the locus coeruleus and neurodegeneration in Alzheimer's disease.
The mechanistic link between selective vulnerability of the locus coeruleus and neurodegeneration in Alzheimer's disease.
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在阿尔茨海默氏病中，基因座的选择性脆弱性与神经退行性的选择性脆弱性之间的机械联系。
DOI：
10.1007/s00401-020-02248-1
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发表时间：
2021-05
影响因子：
12.7
通讯作者：
Murray ME
中科院分区：
文献类型：
--
作者：
Matchett BJ;Grinberg LT;Theofilas P;Murray ME
阿尔茨海默病（AD）的神经病理学特征是细胞内过度磷酸化的tau积聚和细胞外淀粉样蛋白-β斑块沉积，它们以进行性方式影响某些大脑区域。蓝斑核（LC）是脑干脑桥中的一个小核，被广泛认为是阿尔茨海默病中最早形成神经原纤维缠结的部位之一。AD患者在LC中表现出明显的神经元丢失，导致其大小和功能明显减少。LC是中枢神经系统中神经递质去甲肾上腺素（NE）的主要来源，它广泛地支配着大脑的几个区域。考虑到NE是行为的主要调节剂，有助于神经保护和抑制神经炎症，AD中LC的变性和LC - NE系统的最终失调对大脑有不利影响。在这篇综述中，我们详细介绍了LC的神经解剖学和功能，它在神经保护中的重要作用，以及它如何在AD中失调。我们讨论了ad相关的LC神经病理变化和LC神经元选择性易受损伤的机制。此外，我们阐明了局部和投射部位LC去神经支配的神经毒性作用，以及这如何增加疾病病理、进展和严重程度。我们总结了保存LC - ne系统如何用于治疗AD和其他由LC变性影响的神经退行性疾病。
Alzheimer’s disease (AD) is neuropathologically characterized by the intracellular accumulation of hyperphosphorylated tau and the extracellular deposition of amyloid-β plaques, which affect certain brain regions in a progressive manner. The locus coeruleus (LC), a small nucleus in the pons of the brainstem, is widely recognized as one of the earliest sites of neurofibrillary tangle formation in AD. Patients with AD exhibit significant neuronal loss in the LC, resulting in a marked reduction of its size and function. The LC, which vastly innervates several regions of the brain, is the primary source of the neurotransmitter norepinephrine (NE) in the central nervous system. Considering that NE is a major modulator of behavior, contributing to neuroprotection and suppression of neuroinflammation, degeneration of the LC in AD and the ultimate dysregulation of the LC–NE system has detrimental effects in the brain. In this review, we detail the neuroanatomy and function of the LC, its essential role in neuroprotection, and how this is dysregulated in AD. We discuss AD-related neuropathologic changes in the LC and mechanisms by which LC neurons are selectively vulnerable to insult. Further, we elucidate the neurotoxic effects of LC de-innervation both locally and at projection sites, and how this augments disease pathology, progression and severity. We summarize how preservation of the LC–NE system could be used in the treatment of AD and other neurodegenerative diseases affected by LC degeneration.
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影响因子：
12.7
作者：
Braak, Heiko;Del Tredici, Kelly
通讯作者：
Del Tredici, Kelly
影响因子：
6.4
作者：
Bowser, R;Kordower, JH;Mufson, EJ
通讯作者：
Mufson, EJ
DOI：
10.1002/neu.480251107
发表时间：
1994-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
BARBACID, M
通讯作者：
BARBACID, M
影响因子：
5
作者：
Attems, J.;Thomas, A.;Jellinger, K.
通讯作者：
Jellinger, K.
影响因子：
12.7
作者：
Adori, Csaba;Glueck, Laura;Hokfelt, Tomas
通讯作者：
Hokfelt, Tomas