Kim Jun Pyo, Chun Min Young, Kim Soo-Jong, Jang Hyemin, Kim Hee Jin, Jeong Jee Hyang, Na Duk L, Seo Sang Won
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States.
Front Aging Neurosci. 2022 Feb 7;14:829202. doi: 10.3389/fnagi.2022.829202. eCollection 2022.
Previously, sex and apolipoprotein E () genotype had distinct effects on the cognitive trajectory across the Alzheimer's disease (AD) continuum. We therefore aimed to investigate whether these trajectory curves including β-amyloid (Aβ) accumulation in the cortex and striatum, and tau accumulation would differ according to sex and genotype.
We obtained 534 subjects for F-florbetapir (AV45) PET analysis and 163 subjects for F-flortaucipir (AV1451) PET analysis from the Alzheimer's Disease Neuroimaging Initiative database. For cortical Aβ, striatal Aβ, and tau SUVR, we fitted penalized splines to model the slopes of SUVR value as a non-linear function of baseline SUVR value. By integrating the fitted splines, we obtained the predicted SUVR curves as a function of time.
The time from initial SUVR to the cutoff values were 14.9 years for cortical Aβ, 18.2 years for striatal Aβ, and 22.7 years for tau. Although there was no difference in cortical Aβ accumulation rate between women and men, striatal Aβ accumulation was found to be faster in women than in men, and this temporal difference according to sex was more pronounced in tau accumulation. However, ε4 carriers showed faster progression than non-carriers regardless of kinds of AD biomarkers' trajectories.
Our temporal trajectory models illustrate that there is a distinct progression pattern of AD biomarkers depending on sex and genotype. In this regard, our models will be able to contribute to designing personalized treatment and prevention strategies for AD in clinical practice.
此前，性别和载脂蛋白E（）基因型对阿尔茨海默病（AD）连续病程中的认知轨迹有不同影响。因此，我们旨在研究这些轨迹曲线，包括皮质和纹状体中β-淀粉样蛋白（Aβ）的积累以及tau蛋白的积累，是否会因性别和基因型而有所不同。
我们从阿尔茨海默病神经影像倡议数据库中获取了534名用于F-氟比他派（AV45）PET分析的受试者和163名用于F-氟替卡匹（AV1451）PET分析的受试者。对于皮质Aβ、纹状体Aβ和tau标准化摄取值（SUVR），我们拟合了惩罚样条以将SUVR值的斜率建模为基线SUVR值的非线性函数。通过对拟合的样条进行积分，我们获得了作为时间函数的预测SUVR曲线。
从初始SUVR到临界值的时间，皮质Aβ为14.9年，纹状体Aβ为18.2年，tau为22.7年。尽管女性和男性在皮质Aβ积累率上没有差异，但发现女性纹状体Aβ积累比男性更快，并且这种根据性别的时间差异在tau积累中更为明显。然而，无论AD生物标志物轨迹的类型如何，ε4携带者的进展都比非携带者更快。
我们的时间轨迹模型表明，AD生物标志物存在取决于性别和基因型的独特进展模式。在这方面，我们的模型将能够为临床实践中设计个性化的AD治疗和预防策略做出贡献。
