INTRODUCTIONAnimal 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 (FCLC‐MTL) on cortical atrophy across Braak stage regions and its impact on cognition.METHODSWe analyzed functional magnetic resonance imaging and amyloid beta (Aβ) positron emission tomography data from 128 cognitively normal participants, associating novelty‐related FCLC‐MTL with longitudinal atrophy and cognition with and without Aβ moderation.RESULTSCross‐sectionally, lower FCLC‐MTL was associated with atrophy in Braak stage II regions. Longitudinally, atrophy in Braak stage 2 to 4 regions related to lower baseline FCLC‐MTL at elevated levels of Aβ, but not to other regions. Atrophy in Braak stage 2 regions mediated the relation between FCLC‐MTL and subsequent cognitive decline.DISCUSSIONFCLC‐MTL 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.

中文翻译：

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萎缩将较低的新颖性相关蓝斑连接性与临床前 AD 的认知能力下降联系起来

简介 动物研究表明，蓝斑 (LC) 中的 tau 蛋白病理与去甲肾上腺素信号传导减弱、内侧颞叶 (MTL) 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（FCLC-MTL）对 Braak 阶段区域的皮质萎缩及其对认知的影响。方法我们分析了 128 名认知正常参与者的功能性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LC-MTL纵向萎缩和认知，有或没有 Aβ 调节。结果 横断面，FC 较低LC-MTL与 Braak II 期区域的萎缩有关。纵向上，Braak 2 至 4 期区域的萎缩与较低基线 FC 相关LC-MTLAβ 水平升高，但其他区域则不然。 Braak 2 期区域的萎缩介导 FC 与 FC 之间的关系LC-MTL以及随后的认知能力下降。讨论FCLC-MTL与 Aβ 相关的皮质萎缩有关，表明 LC-MTL 连接可以在临床前 AD 中发挥神经保护作用。 新颖相关的功能磁共振成像（fMRI）LC-内侧颞叶（MTL）连接与纵向Aβ依赖性萎缩有关。 随着 Aβ 负担的增加，这种关系延伸到了较高的 Braak 阶段区域。 纵向 MTL 萎缩介导 LC-MTL 连接-认知关系。 我们的研究结果反映了 NE 信号功能障碍后 MTL 萎缩的动物数据。