Dyslipidemia induced large-scale network connectivity abnormality facilitates cognitive decline in the Alzheimer's disease.
Dyslipidemia induced large-scale network connectivity abnormality facilitates cognitive decline in the Alzheimer's disease.
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血脂异常引起的大规模网络连接异常促进阿尔茨海默病的认知能力下降
DOI：
10.1186/s12967-022-03786-w
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发表时间：
2022-12-06
影响因子：
7.4
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Wang Q;Zang F;He C;Zhang Z;Xie C;Alzheimer’s Disease Neuroimaging Initiative
尽管脂质代谢物功能障碍在阿尔茨海默病（AD）的临床体征和病理生理中起着重要作用，但血脂异常如何促进神经病理过程和脑功能损伤进而促进AD的进展尚不清楚。我们将大规模脑静息状态网络（RSNs）方法与典型相关分析相结合，探讨了脂质基因和蛋白质中心水平对脑脊液（CSF）生物标志物、大规模RSNs的动态轨迹和整个AD谱系的认知表现的累积影响。采用支持向量机模型对AD谱进行区分，并采用通径分析检验各变量之间的影响。我们发现脂质途径遗传变异和脂蛋白积累的影响与脑脊液生物标志物水平和阿尔茨海默病谱系中的认知表现显著相关。大规模RSNs的动态轨迹呈现出一种反弹模式，其特征是随着疾病进展，网络内聚连接器作用减弱，网络非内聚省作用增强。重要的是，波动的大尺度rsn连通性与脂质途径遗传变异和脂蛋白、脑脊液生物标志物和认知表现的综合效应显著相关。此外，支持向量机模型显示，脂质相关的22个脑网络连接具有更高的AD频谱分类能力。通路分析进一步发现，血脂异常直接影响脑网络重组或间接影响脑脊液生物标志物，从而导致认知能力下降。血脂异常通过介导大规模脑网络完整性和促进神经病理过程，加重认知能力下降，增加AD的风险。这些发现揭示了脂质代谢在阿尔茨海默病发病机制中的作用，并提示脂质管理是阿尔茨海默病的潜在治疗靶点。在线版本包含补充材料，可在10.1186/s12967-022-03786-w获得。
Although lipid metabolite dysfunction contributes substantially to clinical signs and pathophysiology of Alzheimer’s disease (AD), how dyslipidemia promoting neuropathological processes and brain functional impairment subsequently facilitates the progression of AD remains unclear. We combined large-scale brain resting-state networks (RSNs) approaches with canonical correlation analysis to explore the accumulating effects of lipid gene- and protein-centric levels on cerebrospinal fluid (CSF) biomarkers, dynamic trajectory of large-scale RSNs, and cognitive performance across entire AD spectrum. Support vector machine model was used to distinguish AD spectrum and pathway analysis was used to test the influences among these variables. We found that the effects of accumulation of lipid-pathway genetic variants and lipoproteins were significantly correlated with CSF biomarkers levels and cognitive performance across the AD spectrum. Dynamic trajectory of large-scale RSNs represented a rebounding mode, which is characterized by a weakened network cohesive connector role and enhanced network incohesive provincial role following disease progression. Importantly, the fluctuating large-scale RSNs connectivity was significantly correlated with the summative effects of lipid-pathway genetic variants and lipoproteins, CSF biomarkers, and cognitive performance. Moreover, SVM model revealed that the lipid-associated twenty-two brain network connections represented higher capacity to classify AD spectrum. Pathway analysis further identified dyslipidemia directly influenced brain network reorganization or indirectly affected the CSF biomarkers and subsequently caused cognitive decline. Dyslipidemia exacerbated cognitive decline and increased the risk of AD via mediating large-scale brain networks integrity and promoting neuropathological processes. These findings reveal a role for lipid metabolism in AD pathogenesis and suggest lipid management as a potential therapeutic target for AD. The online version contains supplementary material available at 10.1186/s12967-022-03786-w.
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tau，淀粉样蛋白和级联网络失败在阿尔茨海默氏病谱系中。
DOI：
10.1016/j.cortex.2017.09.018
发表时间：
2017-12
期刊：
Cortex; a journal devoted to the study of the nervous system and behavior
影响因子：
--
作者：
Jones DT;Graff-Radford J;Lowe VJ;Wiste HJ;Gunter JL;Senjem ML;Botha H;Kantarci K;Boeve BF;Knopman DS;Petersen RC;Jack CR Jr
通讯作者：
Jack CR Jr
影响因子：
3.7
作者：
Goveas JS;Xie C;Chen G;Li W;Ward BD;Franczak MB;Jones JL;Antuono PG;Li SJ
通讯作者：
Li SJ
影响因子：
16.2
作者：
Bai, Bing;Wang, Xusheng;Peng, Junmin
通讯作者：
Peng, Junmin
影响因子：
4.2
作者：
Armstrong, Nicole M.;An, Yang;Resnick, Susan M.
通讯作者：
Resnick, Susan M.
影响因子：
16.6
作者：
通讯作者：
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