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皮质白质中明显的小胶质细胞激活与原发性进行性失语症的皮质萎缩呈选择性相关。

Prominent microglial activation in cortical white matter is selectively associated with cortical atrophy in primary progressive aphasia.

机构信息

Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

出版信息

Neuropathol Appl Neurobiol. 2019 Apr;45(3):216-229. doi: 10.1111/nan.12494. Epub 2018 May 17.

DOI:10.1111/nan.12494
PMID:29679378
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6196127/
Abstract

AIMS

Primary progressive aphasia (PPA) is a clinical syndrome characterized by selective language impairments associated with focal cortical atrophy favouring the language dominant hemisphere. PPA is associated with Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and significant accumulation of activated microglia. Activated microglia can initiate an inflammatory cascade that may contribute to neurodegeneration, but their quantitative distribution in cortical white matter and their relationship with cortical atrophy remain unknown. We investigated white matter activated microglia and their association with grey matter atrophy in 10 PPA cases with either AD or FTLD-TDP pathology.

METHODS

Activated microglia were quantified with optical density measures of HLA-DR immunoreactivity in two regions with peak cortical atrophy, and one nonatrophied region within the language dominant hemisphere of each PPA case. Nonatrophied contralateral homologues of the language dominant regions were examined for hemispheric asymmetry.

RESULTS

Qualitatively, greater densities of activated microglia were observed in cortical white matter when compared to grey matter. Quantitative analyses revealed significantly greater densities of activated microglia in the white matter of atrophied regions compared to nonatrophied regions in the language dominant hemisphere (P < 0.05). Atrophied regions of the language dominant hemisphere also showed significantly more activated microglia compared to contralateral homologues (P < 0.05).

CONCLUSIONS

White matter activated microglia accumulate more in atrophied regions in the language dominant hemisphere of PPA. While microglial activation may constitute a response to neurodegenerative processes in white matter, the resultant inflammatory processes may also exacerbate disease progression and contribute to cortical atrophy.

摘要

目的

原发性进行性失语症（PPA）是一种以选择性语言障碍为特征的临床综合征，与优势半球的局灶性皮质萎缩有关。PPA 与阿尔茨海默病（AD）、额颞叶变性（FTLD）和大量激活的小胶质细胞积聚有关。激活的小胶质细胞可以引发炎症级联反应，从而导致神经退行性变，但它们在皮质白质中的定量分布及其与皮质萎缩的关系尚不清楚。我们研究了 10 例 PPA 病例（AD 或 FTLD-TDP 病理）皮质白质中激活的小胶质细胞及其与灰质萎缩的关系。

方法

用 HLA-DR 免疫反应的光密度测量值在两个皮质萎缩峰值区域和每个 PPA 病例优势半球的一个非萎缩区域中量化激活的小胶质细胞。检查非萎缩的优势半球语言区域的同型物以评估半球不对称性。

结果

与灰质相比，皮质白质中观察到的激活小胶质细胞密度更高。定量分析显示，与优势半球非萎缩区域相比，萎缩区域的皮质白质中激活的小胶质细胞密度显著增加（P<0.05）。优势半球萎缩区域的激活小胶质细胞也明显多于对侧同型物（P<0.05）。

结论

PPA 优势半球萎缩区域的白质中积累了更多的激活小胶质细胞。虽然小胶质细胞激活可能构成对白质神经退行性过程的反应，但由此产生的炎症过程也可能加剧疾病进展并导致皮质萎缩。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/6196127/59555852bbad/nihms962034f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/6196127/4822265cefd7/nihms962034f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/6196127/91cd53b18834/nihms962034f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/6196127/fa3805c57289/nihms962034f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/6196127/59555852bbad/nihms962034f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/6196127/4822265cefd7/nihms962034f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/6196127/91cd53b18834/nihms962034f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/6196127/fa3805c57289/nihms962034f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/6196127/59555852bbad/nihms962034f4.jpg

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2
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3
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5
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