Single Nucleotide Polymorphisms in Alzheimer's Disease Risk Genes Are Associated with Intrinsic Connectivity in Middle Age.
Single Nucleotide Polymorphisms in Alzheimer's Disease Risk Genes Are Associated with Intrinsic Connectivity in Middle Age.
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DOI：
10.3233/jad-200444
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发表时间：
2020-09
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影响因子：
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通讯作者：
Jenna Katherine Blujus;Laura Elizabeth Korthauer;Elizabeth Awe;Marijam Frahmand;I. Driscoll
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作者：
Jenna Katherine Blujus;Laura Elizabeth Korthauer;Elizabeth Awe;Marijam Frahmand;I. Driscoll
背景在阿尔茨海默病(AD)病程的早期，如中年，最好在临床症状出现之前识别出阿尔茨海默病(AD)的高危个体，这一点至关重要，因为那时的干预措施可能会更成功。全基因组关联和候选基因研究已经发现APOE、CLU、CR1、PICALM和SORL1的单核苷酸多态(SNPs)会增加AD的风险。目的在本研究中，我们研究了这些基因的SNPs与默认模式网络(DMN)、额顶控制网络(FPN)和执行控制网络(ECN)中静息态功能连接的关系。方法采用模板匹配法通过独立成分分析识别感兴趣的静息状态网络，并采用双重回归方法提取个体空间地图和时间进程。结果在DMN后部，CR1 rs1408077和CLU rs9331888基因多态性与功能连接性相关(P<0.05)。结论首次证实了健康中年人CLU、CR1和SORL1的固有网络连通性与AD风险等位基因的关系。这些SNPs应该被考虑在未来的研究中，目的是确定潜在的AD临床前生物标记物。
BACKGROUND It is critical to identify individuals at risk for Alzheimer's disease (AD) earlier in the disease time course, such as middle age and preferably well prior to the onset of clinical symptoms, when intervention efforts may be more successful. Genome-wide association and candidate gene studies have identified single nucleotide polymorphisms (SNPs) in APOE, CLU, CR1, PICALM, and SORL1 that confer increased risk of AD. OBJECTIVE In the current study, we investigated the associations between SNPs in these genes and resting-state functional connectivity within the default mode network (DMN), frontoparietal control network (FPN), and executive control network (ECN) in healthy, non-demented middle-aged adults (age 40 -60; N = 123; 74 females). METHODS Resting state networks of interest were identified through independent components analysis using a template-matching procedure and individual spatial maps and time courses were extracted using dual regression. RESULTS Within the posterior DMN, functional connectivity was associated with CR1 rs1408077 and CLU rs9331888 polymorphisms (ps 0.05). CONCLUSION This is the first demonstration of the relationship between intrinsic network connectivity and AD risk alleles in CLU, CR1, and SORL1 in healthy, middle-aged adults. These SNPs should be considered in future investigations aimed at identifying potential preclinical biomarkers for AD.