JNNP-额叶痴呆患者,大脑中tau蛋白不均匀分布

2021-07-07 Freeman MedSci原创

-额叶痴呆患者,大脑中tau蛋白不均匀分布

阿尔茨海默病的行为变异型(bvAD,以前称为 "额叶AD")患者早期会出现突出的行为症状和人格变化,如抑制、强迫性行为和丧失同情心。这些人在临床上让人联想到行为变异性额颞叶痴呆(bvFTD),但以AD为主要病理特征,在神经解剖学上类似于 "典型 "AD(tAD)患者,因为bvAD的萎缩和低代谢模式主要发生在颞顶区。影像学和病理学调查(主要是病例报告或基于这种表型的低发病率的小型队列研究)提供了关于bvAD中额叶皮质参与的混合结果。

这种明显的临床解剖学差异表明,需要更好地了解bvAD表型的神经生物学因素。为此,研究bvAD中tau沉积的分布是至关重要的,因为AD的这一中心神经病理学标志与认知症状的类型和严重程度密切相关,并且先于和预测MRI和[18F]-氟脱氧葡萄糖(FDG)正电子发射断层扫描(PET)检测到的神经变性模式。

藉此,阿姆斯特丹大学的Ellen Singleton等人,探究了bvAD中tau病理的区域分布:利用正电子发射断层扫描(PET)和尸检,调查了bvAD体内和体外tau沉积的分布。

对于tau的PET研究,7名淀粉样β阳性的bvAD患者接受[18F]flortaucipir或[18F]RO948 PET。他们将tau PET摄取值转换为标准化的(W-)分数,调整了年龄、性别和 "典型 "记忆为主的AD组(n=205)的迷你精神状态检查。

W-scores是在内侧、颞顶、内侧和外侧前额、岛叶和全脑感兴趣的区域、额叶到内侧和额叶到顶叶的比率以及内在功能连接网络模板中计算的。

在死后研究中,海马CA1、颞叶、顶叶、额叶和岛叶皮质中AT8(tau)阳性区域的百分比在尸检证实的bvAD(n=8)和典型AD(tAD;n=7)患者之间进行比较。

他们发现,在三个病例中观察到个别区域W-scores≥1.96(相当于P<0.05),即5号病例:内侧前额皮层(W=2.13)和前部默认模式网络(W=3.79),2号病例:外侧前额皮层(W=2.79)和显著性网络(W=2.77),以及7号病例:额叶与视丘比(W=2.04)。其余4个病例都属于tAD组的正常分布范围。

尸检时AT8染色表明,bvAD和tAD之间的磷酸化tau水平没有组级区域差异(所有P>0.05)。

这个研究的重要意义在于:无论是体内还是体外,bvAD患者都表现出tau病理的异质性分布。由于参与行为调节的关键区域并不总是受到tau病理学的不成比例的影响,其他因素更可能驱动bvAD的临床表型。

原文出处:
Singleton E, Hansson O, Pijnenburg YAL, La Joie R, Mantyh WG, Tideman P, Stomrud E, Leuzy A, Johansson M, Strandberg O, Smith R, Berendrecht E, Miller BL, Iaccarino L, Edwards L, Strom A, Wolters EE, Coomans E, Visser D, Golla SSV, Tuncel H, Bouwman F, Van Swieten JC, Papma JM, van Berckel B, Scheltens P, Dijkstra AA, Rabinovici GD, Ossenkoppele R. Heterogeneous distribution of tau pathology in the behavioural variant of Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2021 Apr 13:jnnp-2020-325497. doi: 10.1136/jnnp-2020-325497. Epub ahead of print. PMID: 33850001.

 
 
 
 

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    2021-07-08 hb2008ye
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    2021-07-07 ms3000002052890081

    学习

    0

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    2021-07-07 junJUN

    老年人痴呆何药可用??

    0

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