Pathological Characterisation of Posterior Cortical Atrophy in Comparison With Amnestic Alzheimer's Disease.

IF 4 2区 医学 Q1 CLINICAL NEUROLOGY
Z Abdi, K X Yong, J M Schott, A Gatt, T Revesz, S J Crutch, T Lashley
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引用次数: 0

Abstract

Aims: Posterior cortical atrophy (PCA) is a predominantly young-onset neurodegenerative syndrome, typically caused by Alzheimer's disease (PCA-AD). PCA-AD presents with visual and spatial dysfunction attributed to occipito-parietal or 'posterior' brain regions rather than memory difficulties characteristic of typical amnestic-led Alzheimer's disease (a-AD) attributed to medial temporal regions. Imaging and neuropathological studies suggest that PCA-AD is associated with a more posterior distribution of tau neurofibrillary tangles (NFTs), whereas β-amyloid pathology (Aβ) is diffusely deposited throughout the cortex. This study characterised the neuropathological substrates of PCA-AD in comparison with a-AD, to further understanding of the biological basis of phenotypical heterogeneity in AD.

Methods: Immunohistochemistry for Aβ; tau; the microglial markers CD68, CR3-43 and Iba1; α-synuclein; and TDP-43 was carried out on 26 PCA-AD and 27 age and gender-matched a-AD cases at the Queen Square Brain Bank. Aβ, tau and the three microglial markers were quantified in the superior frontal, superior temporal, superior parietal and occipital (primary visual cortex) cortices, with α-synuclein and TDP-43 assessed using formal staging criteria. In addition, microglial circularity, a morphological indicator of microglial activation state, was calculated.

Results: There was a higher load of Aβ and tau in the parietal region of PCA-AD compared to a-AD. In the PCA-AD compared to the a-AD group, there were significant increases in tau load in parietal and frontal relative to temporal regions. There was no difference in cerebral amyloid angiopathy (CAA) severity between PCA-AD and a-AD. There was a significantly lower temporal CD68 load in a-AD compared with PCA-AD. In a-AD, CD68 load was lowest and tau load highest in the temporal relative to all other regions.

Conclusions: This study demonstrates differences in the distribution of Aβ and tau and variations in regional neuroinflammatory response in PCA-AD and a-AD. These findings extend our understanding of the biological substrates underpinning PCA-AD and highlight the potential for exploring phenotypic variants to understand selective vulnerability in neurodegenerative diseases.

目的:后皮质萎缩(PCA)是一种主要由阿尔茨海默病(PCA-AD)引起的年轻发病的神经退行性综合征。PCA-AD 表现为视觉和空间功能障碍,归因于枕顶叶或 "后部 "脑区,而不是典型的失忆性阿尔茨海默病(a-AD)所特有的记忆障碍,归因于颞内侧脑区。影像学和神经病理学研究表明,PCA-AD 与 tau 神经纤维缠结(NFTs)的后部分布有关,而 β 淀粉样病理(Aβ)则在整个大脑皮层弥漫沉积。本研究比较了PCA-AD与a-AD的神经病理学基础,以进一步了解AD表型异质性的生物学基础:方法:对皇后广场脑库(Queen Square Brain Bank)的26例PCA-AD和27例年龄和性别匹配的a-AD病例进行了Aβ、tau、小胶质细胞标记物CD68、CR3-43和Iba1、α-突触核蛋白和TDP-43的免疫组化。对额叶上部、颞叶上部、顶叶上部和枕叶(初级视觉皮层)皮层的 Aβ、tau 和三种小胶质细胞标记物进行了量化,并使用正式的分期标准对α-突触核蛋白和 TDP-43 进行了评估。此外,还计算了小胶质细胞的圆周率(小胶质细胞活化状态的形态学指标):结果:与a-AD相比,PCA-AD顶叶区的Aβ和tau含量更高。与 a-AD 组相比,PCA-AD 组顶叶和额叶的 tau 负荷明显高于颞叶。PCA-AD组和a-AD组的脑淀粉样血管病(CAA)严重程度没有差异。与 PCA-AD 相比,a-AD 的颞叶 CD68 负荷明显较低。在a-AD中,相对于所有其他区域,颞部的CD68载量最低,tau载量最高:结论:这项研究表明,在 PCA-AD 和 a-AD 中,Aβ 和 tau 的分布存在差异,区域神经炎症反应也存在差异。这些研究结果拓展了我们对 PCA-AD 的生物学基础的认识,并突出了探索表型变异以了解神经退行性疾病中选择性易感性的潜力。
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来源期刊
CiteScore
8.20
自引率
2.00%
发文量
87
审稿时长
6-12 weeks
期刊介绍: Neuropathology and Applied Neurobiology is an international journal for the publication of original papers, both clinical and experimental, on problems and pathological processes in neuropathology and muscle disease. Established in 1974, this reputable and well respected journal is an international journal sponsored by the British Neuropathological Society, one of the world leading societies for Neuropathology, pioneering research and scientific endeavour with a global membership base. Additionally members of the British Neuropathological Society get 50% off the cost of print colour on acceptance of their article.
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