Neuroinflammation is independently associated with brain network dysfunction in Alzheimer's disease.
Neuroinflammation is independently associated with brain network dysfunction in Alzheimer's disease.
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DOI：
10.1038/s41380-022-01878-z
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发表时间：
2023-03
影响因子：
11
通讯作者：
Edison, Paul
中科院分区：
文献类型：
--
作者：
Leng, Fangda;Hinz, Rainer;Gentleman, Steve;Hampshire, Adam;Dani, Melanie;Brooks, David J.;Edison, Paul
脑网络功能障碍在阿尔茨海默病(AD)中得到越来越多的认识。然而，大脑连接中断的原因仍然知之甚少。近年来，神经炎症被认为是AD发病的重要因素。小胶质细胞参与构建和维持健康的神经元网络，但促炎的小胶质细胞也可以破坏这些网络。我们假设，小胶质细胞的激活与AD的脑连接中断独立相关。我们进行了一项横断面多模式成像研究，并询问了神经炎症的成像生物标志物、Aβ沉积、脑连接和认知之间的关系。42名受试者(12名Aβ阳性的受试者、14名Aβ阳性的AD患者和16名Aβ阴性的健康对照组)被纳入研究。受试者用11C-PBR28和18F-氟美他莫PET定量Aβ沉积和小胶质细胞激活，T1加权、弥散张量和静息状态功能磁共振成像评估结构网络和功能网络。比较不同诊断组间的11C-PBR28摄取、结构网络完整性和功能网络组织化，并对26例Aβ阳性患者进行神经炎症与脑网络的关系检验。AD患者11C-PBR28摄取增加，FA减少，网络小世界和局部有效率增加。皮质11C-PBR28摄取与结构完整性(标准化β = −0.375，p = 0.037)和网络局部效率(标准化β = −0.468，p <； 0.001)负相关，与皮质厚度和Aβ沉积无关，而Aβ不相关。网络结构完整性、小世界和局部效率、皮质厚度与认知呈正相关。我们的发现表明，皮质神经炎与结构和功能网络的破坏一致，与Aβ和皮质萎缩无关。这些发现将阿尔茨海默病的大脑连接性变化与病理过程联系起来，并提示了一条从神经炎症到全身性脑功能障碍的途径。
Brain network dysfunction is increasingly recognised in Alzheimer’s disease (AD). However, the causes of brain connectivity disruption are still poorly understood. Recently, neuroinflammation has been identified as an important factor in AD pathogenesis. Microglia participate in the construction and maintenance of healthy neuronal networks, but pro-inflammatory microglia can also damage these circuits. We hypothesised that microglial activation is independently associated with brain connectivity disruption in AD. We performed a cross-sectional multimodal imaging study and interrogated the relationship between imaging biomarkers of neuroinflammation, Aβ deposition, brain connectivity and cognition. 42 participants (12 Aβ-positive MCI, 14 Aβ-positive AD and 16 Aβ-negative healthy controls) were recruited. Participants had 11C-PBR28 and 18F-flutemetamol PET to quantify Aβ deposition and microglial activation, T1-weighted, diffusion tensor and resting-state functional MRI to assess structural network and functional network. 11C-PBR28 uptake, structural network integrity and functional network orgnisation were compared across diagnostic groups and the relationship between neuroinflammation and brain network was tested in 26 Aβ-positive patients. Increased 11C-PBR28 uptake, decreased FA, network small-worldness and local efficiency were observed in AD patients. Cortical 11C-PBR28 uptake correlated negatively with structural integrity (standardised β = −0.375, p = 0.037) and network local efficiency (standardised β = −0.468, p < 0.001), independent of cortical thickness and Aβ deposition, while Aβ was not. Network structural integrity, small-worldness and local efficiency, and cortical thickness were positively associated with cognition. Our findings suggest cortical neuroinflammation coincide with structural and functional network disruption independent of Aβ and cortical atrophy. These findings link the brain connectivity change and pathological process in Alzheimer’s disease, and suggest a pathway from neuroinflammation to systemic brain dysfunction.
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影响因子：
34.7
作者：
Frost, Bess;Diamond, Marc I.
通讯作者：
Diamond, Marc I.
影响因子：
6.1
作者：
Edison, Paul;Archer, Hilary A.;Brooks, David J.
通讯作者：
Brooks, David J.
DOI：
10.1073/pnas.0308627101
发表时间：
2004-03-30
影响因子：
11.1
作者：
Greicius, MD;Srivastava, G;Menon, V
通讯作者：
Menon, V
影响因子：
4.2
作者：
Gold BT;Zhu Z;Brown CA;Andersen AH;LaDu MJ;Tai L;Jicha GA;Kryscio RJ;Estus S;Nelson PT;Scheff SW;Abner E;Schmitt FA;Van Eldik LJ;Smith CD
通讯作者：
Smith CD
影响因子：
3.7
作者：
Jones L;Holmans PA;Hamshere ML;Harold D;Moskvina V;Ivanov D;Pocklington A;Abraham R;Hollingworth P;Sims R;Gerrish A;Pahwa JS;Jones N;Stretton A;Morgan AR;Lovestone S;Powell J;Proitsi P;Lupton MK;Brayne C;Rubinsztein DC;Gill M;Lawlor B;Lynch A;Morgan K;Brown KS;Passmore PA;Craig D;McGuinness B;Todd S;Holmes C;Mann D;Smith AD;Love S;Kehoe PG;Mead S;Fox N;Rossor M;Collinge J;Maier W;Jessen F;Schürmann B;Heun R;Kölsch H;van den Bussche H;Heuser I;Peters O;Kornhuber J;Wiltfang J;Dichgans M;Frölich L;Hampel H;Hüll M;Rujescu D;Goate AM;Kauwe JS;Cruchaga C;Nowotny P;Morris JC;Mayo K;Livingston G;Bass NJ;Gurling H;McQuillin A;Gwilliam R;Deloukas P;Al-Chalabi A;Shaw CE;Singleton AB;Guerreiro R;Mühleisen TW;Nöthen MM;Moebus S;Jöckel KH;Klopp N;Wichmann HE;Rüther E;Carrasquillo MM;Pankratz VS;Younkin SG;Hardy J;O'Donovan MC;Owen MJ;Williams J
通讯作者：
Williams J