Does Alzheimer's disease begin in the brainstem?
Does Alzheimer's disease begin in the brainstem?
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DOI：
10.1111/j.1365-2990.2009.01038.x
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发表时间：
2009-12
影响因子：
5
通讯作者：
Hof PR
中科院分区：
文献类型：
--
作者：
Simic G;Stanic G;Mladinov M;Jovanov-Milosevic N;Kostovic I;Hof PR
尽管大量证据表明，神经元细胞骨架病理变化的进展在决定阿尔茨海默病（AD）痴呆的严重程度方面至关重要，但这些变化的确切原因和进化、它们开始的初始位置以及它们发展的神经元易感性水平尚不清楚。目前诊断阿尔茨海默病的临床标准主要集中在海马和高阶新皮质区功能障碍引起的认知缺陷上，而痴呆症的非认知、行为和心理症状，如情绪、情绪、食欲、觉醒-睡眠周期、精神错乱、躁动和抑郁等，很少被考虑。这些症状的早期出现表明脑干受累，更具体地说，是5 -羟色胺能核受累。尽管Braak分期系统和NIA-RI标准不包括它们的评估，但最近的一些报道引起了人们对中缝核，特别是中缝背核（DRN）在AD发病机制中选择性和早期受累的可能性的关注。基于这些差异易感性和解剖学连通性的发现，提出了一种新的阿尔茨海默病进展的发病机制。尽管神经原纤维变性的确切机制仍有待阐明，但我们推测累积性氧化损伤可能是DRN改变的主要原因，因为年龄是散发性AD的主要危险因素。在这样的框架下，β -淀粉样蛋白的产生仅被认为是促进ad相关神经病理改变的分子系列事件的因素之一（尽管在家族病例中是一个重要因素）。
Although substantial evidence indicates that the progression of pathological changes of the neuronal cytoskeleton is crucial in determining the severity of dementia in Alzheimer's disease (AD), the exact causes and evolution of these changes, the initial site at which they begin, and the neuronal susceptibility levels for their development are poorly understood. The current clinical criteria for diagnosis of AD are focused mostly on cognitive deficits produced by dysfunction of hippocampal and high-order neocortical areas, whereas non-cognitive, behavioural, and psychological symptoms of dementia such as disturbances in mood, emotion, appetite, and wake-sleep cycle, confusion, agitation, and depression, have been less considered. The early occurrence of these symptoms suggests brainstem involvement, and more specifically of the serotonergic nuclei. In spite of the fact that the Braak staging system and NIA-RI criteria do not include their evaluation, several recent reports drew attention to the possibility of selective and early involvement of raphe nuclei, particularly the dorsal raphe nucleus (DRN), in the pathogenesis of AD. Based on these findings of differential susceptibility and anatomical connectivity, a novel pathogenetic scheme of AD progression was proposed. Although the precise mechanisms of neurofibrillary degeneration still await elucidation, we speculated that cumulative oxidative damage may be the main cause of DRN alterations, as the age is the main risk factor for sporadic AD. Within such a framework, β–amyloid production is considered only as one of the factors (although a significant one in familial cases) that promotes molecular series of events underlying AD-related neuropathological changes.
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DOI：
10.1083/jcb.115.3.717
发表时间：
1991-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Butner KA;Kirschner MW
通讯作者：
Kirschner MW
影响因子：
4.2
作者：
den Dunnen, Wilfred F. A.;Brouwer, Wiebo H.;Holstege, Gert
通讯作者：
Holstege, Gert
影响因子：
9.9
作者：
ARRIAGADA, PV;GROWDON, JH;HYMAN, BT
通讯作者：
HYMAN, BT
影响因子：
2.9
作者：
ANDREADIS, A;BROWN, WM;KOSIK, KS
通讯作者：
KOSIK, KS
影响因子：
2.5
作者：
BRILLIANT, M;ELBLE, RJ;STRUBLE, RG
通讯作者：
STRUBLE, RG