Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status.
Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status.
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DOI：
10.1186/s13195-023-01380-w
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发表时间：
2024-01-11
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影响因子：
--
通讯作者：
中科院分区：
文献类型：
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APOE 4是散发性阿尔茨海默病（AD）最强的遗传风险因子，而APOE 2则具有保护作用。然而，APOE对认知完整个体神经退行性变的影响，以及这些相关性如何随着认知能力下降而演变，目前尚不清楚。此外，很少有研究评估APOE对神经退行性变化的影响是否受到其他AD关键风险因素（包括年龄和性别）的影响。参与者包括来自Rancho Bernardo健康老化研究和加州大学圣地亚哥阿尔茨海默病研究中心的老年人（57%为女性; 77 ± 7岁），包括192名认知正常（CN）个体和33名轻度认知障碍个体。受试者接受了弥散MRI，并计算了白色物质、灰质和皮质下感兴趣区域的多室限制性频谱成像（RSI）指标。参与者分为APOE 4携带者、APOE 2携带者和APOE 3纯合子。CN之间的协方差分析（调整年龄，性别和扫描仪）评估了APOE的大脑微结构差异，以及APOE和性别之间的相互作用。对所有参与者的分析研究了APOE 4与认知状态之间的相互作用。线性回归评估APOE与年龄的相互作用。在CN中，APOE 4携带者表现出较低的内嗅皮层神经突起密度比非携带者，而APOE 2携带者表现出较低的扣带回神经突起密度比非携带者。APOE 4的内嗅微结构和APOE 2的内嗅和扣带回微结构的差异仅存在于女性。年龄与APOE 4非携带者中较低的内嗅限制性各向同性扩散相关，而年龄与APOE 4携带者中较低的壳核限制性各向同性扩散相关。认知正常和受损的参与者之间的微观结构的差异更强的APOE 4载体在内侧颞区，丘脑和全球灰质，但更强的非载体在尾状核。内嗅皮质可能是症状前个体中与APOE 4相关的神经退行性变化的早期靶点，而APOE 2可能支持有益的白色物质和内嗅微结构，潜在的性别差异值得进一步研究。APOE改变了与衰老和认知障碍相关的微结构模式，这可能会促进生物标志物的开发，以区分正常脑老化，APOE依赖性途径和非AD病因的微结构变化特征。在线版本包含补充材料，可通过10.1186/s13195-023-01380-w获得。
APOE4 is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD), whereas APOE2 confers protection. However, effects of APOE on neurodegeneration in cognitively intact individuals, and how these associations evolve with cognitive decline, are unclear. Furthermore, few studies have evaluated whether effects of APOE on neurodegenerative changes are modified by other AD key risk factors including age and sex. Participants included older adults (57% women; 77 ± 7 years) from the Rancho Bernardo Study of Health Aging and the University of California San Diego Alzheimer’s Disease Research Center, including 192 cognitively normal (CN) individuals and 33 with mild cognitive impairment. Participants underwent diffusion MRI, and multicompartment restriction spectrum imaging (RSI) metrics were computed in white matter, gray matter, and subcortical regions of interest. Participants were classified as APOE4 carriers, APOE2 carriers, and APOE3 homozygotes. Analysis of covariance among CN (adjusting for age, sex, and scanner) assessed differences in brain microstructure by APOE, as well as interactions between APOE and sex. Analyses across all participants examined interactions between APOE4 and cognitive status. Linear regressions assessed APOE by age interactions. Among CN, APOE4 carriers showed lower entorhinal cortex neurite density than non-carriers, whereas APOE2 carriers showed lower cingulum neurite density than non-carriers. Differences in entorhinal microstructure by APOE4 and in entorhinal and cingulum microstructure by APOE2 were present for women only. Age correlated with lower entorhinal restricted isotropic diffusion among APOE4 non-carriers, whereas age correlated with lower putamen restricted isotropic diffusion among APOE4 carriers. Differences in microstructure between cognitively normal and impaired participants were stronger for APOE4-carriers in medial temporal regions, thalamus, and global gray matter, but stronger for non-carriers in caudate. The entorhinal cortex may be an early target of neurodegenerative changes associated with APOE4 in presymptomatic individuals, whereas APOE2 may support beneficial white matter and entorhinal microstructure, with potential sex differences that warrant further investigation. APOE modifies microstructural patterns associated with aging and cognitive impairment, which may advance the development of biomarkers to distinguish microstructural changes characteristic of normal brain aging, APOE-dependent pathways, and non-AD etiologies. The online version contains supplementary material available at 10.1186/s13195-023-01380-w.
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年龄较大的社区居民男女之间的年龄与大脑微观结构之间的关联：兰乔·伯纳多（Rancho Bernardo）研究。
影响因子：
4.2
作者：
Reas ET;Hagler DJ Jr;Andrews MJ;Lee RR;Dale AM;McEvoy LK
通讯作者：
McEvoy LK
DOI：
10.1523/jneurosci.3252-09.2009
发表时间：
2009-12-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fjell AM;Walhovd KB;Fennema-Notestine C;McEvoy LK;Hagler DJ;Holland D;Brewer JB;Dale AM
通讯作者：
Dale AM
DOI：
10.1016/j.bpsc.2019.05.017
发表时间：
2019-11-01
影响因子：
5.9
作者：
Karcher, Nicole R.;Rogers, Baxter P.;Woodward, Neil D.
通讯作者：
Woodward, Neil D.
影响因子：
7.2
作者：
McDowell, I;Kristjansson, B;Hebert, R
通讯作者：
Hebert, R
影响因子：
4.2
作者：
Adluru, Nagesh;Destiche, Daniel J.;Bendlin, Barbara B.
通讯作者：
Bendlin, Barbara B.