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萎缩与较低的新奇相关蓝斑连接与临床前 AD 的认知能力下降有关。

Atrophy links lower novelty-related locus coeruleus connectivity to cognitive decline in preclinical AD.

机构信息

Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Harvard Medical School, Boston, Massachusetts, USA.

出版信息

Alzheimers Dement. 2024 Jun;20(6):3958-3971. doi: 10.1002/alz.13839. Epub 2024 Apr 27.

DOI:10.1002/alz.13839
PMID:38676563
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11180940/
Abstract

INTRODUCTION

Animal research has shown that tau pathology in the locus coeruleus (LC) is associated with reduced norepinephrine signaling, lower projection density to the medial temporal lobe (MTL), atrophy, and cognitive impairment. We investigated the contribution of LC-MTL functional connectivity (FC) on cortical atrophy across Braak stage regions and its impact on cognition.

METHODS

We analyzed functional magnetic resonance imaging and amyloid beta (Aβ) positron emission tomography data from 128 cognitively normal participants, associating novelty-related FC with longitudinal atrophy and cognition with and without Aβ moderation.

RESULTS

Cross-sectionally, lower FC was associated with atrophy in Braak stage II regions. Longitudinally, atrophy in Braak stage 2 to 4 regions related to lower baseline FC at elevated levels of Aβ, but not to other regions. Atrophy in Braak stage 2 regions mediated the relation between FC and subsequent cognitive decline.

DISCUSSION

FC is implicated in Aβ-related cortical atrophy, suggesting that LC-MTL connectivity could confer neuroprotective effects in preclinical AD.

HIGHLIGHTS

Novelty-related functional magnetic resonance imaging (fMRI) LC-medial temporal lobe (MTL) connectivity links to longitudinal Aβ-dependent atrophy. This relationship extended to higher Braak stage regions with increasing Aβ burden. Longitudinal MTL atrophy mediated the LC-MTL connectivity-cognition relationship. Our findings mirror the animal data on MTL atrophy following NE signal dysfunction.

摘要

简介

动物研究表明，蓝斑核（LC）中的 tau 病理学与去甲肾上腺素信号降低、向内侧颞叶（MTL）的投射密度降低、萎缩和认知障碍有关。我们研究了 LC-MTL 功能连接（FC）对跨 Braak 阶段区域皮质萎缩的贡献及其对认知的影响。

方法

我们分析了 128 名认知正常参与者的功能磁共振成像和淀粉样蛋白β（Aβ）正电子发射断层扫描数据，将新颖性相关的 FC 与纵向萎缩以及 Aβ 调节下的认知和无 Aβ调节的认知相关联。

结果

在横断面上，较低的 FC 与 Braak 阶段 II 区域的萎缩有关。在纵向，Braak 阶段 2 到 4 区域的萎缩与 Aβ 水平升高时的基线 FC 较低有关，但与其他区域无关。Braak 阶段 2 区域的萎缩介导了 FC 与随后认知下降之间的关系。

讨论

FC 与 Aβ 相关的皮质萎缩有关，这表明 LC-MTL 连接可能在临床前 AD 中提供神经保护作用。

重点

新颖性相关功能磁共振成像（fMRI）LC-内侧颞叶（MTL）连接与纵向 Aβ 依赖性萎缩有关。这种关系扩展到 Aβ 负荷增加时更高的 Braak 阶段区域。纵向 MTL 萎缩介导了 LC-MTL 连接与认知的关系。我们的发现与动物研究中 NE 信号功能障碍后 MTL 萎缩的结果相呼应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33ac/11180940/bfd111669014/ALZ-20-3958-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33ac/11180940/e138201fcaee/ALZ-20-3958-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33ac/11180940/ff3c936c354f/ALZ-20-3958-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33ac/11180940/8617b740cb21/ALZ-20-3958-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33ac/11180940/a0eb3d50a548/ALZ-20-3958-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33ac/11180940/bfd111669014/ALZ-20-3958-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33ac/11180940/e138201fcaee/ALZ-20-3958-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33ac/11180940/ff3c936c354f/ALZ-20-3958-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33ac/11180940/8617b740cb21/ALZ-20-3958-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33ac/11180940/a0eb3d50a548/ALZ-20-3958-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33ac/11180940/bfd111669014/ALZ-20-3958-g001.jpg

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