The association between white matter hyperintensities and amyloid and tau deposition
The association between white matter hyperintensities and amyloid and tau deposition
复制标题
DOI：
10.1016/j.nicl.2023.103383
复制
发表时间：
2023-03-23
影响因子：
4.2
通讯作者：
Choupan, Jeiran
中科院分区：
文献类型：
--
作者：
Alban, Sierra L.;Lynch, Kirsten M.;Choupan, Jeiran
脑白质高信号(WMH)常见于阿尔茨海默病(AD)，并与脑缺血有关，但其与β-淀粉样蛋白和心血管危险因子(CVRF)的关系尚不完全清楚。我们使用AT分类根据β-淀粉样蛋白和tau蛋白的病理情况对个体进行分类，然后评估β-淀粉样蛋白和tau蛋白对WMH体积和数量的影响。然后，我们确定了β-淀粉样蛋白和WMH积聚相关的区域。最后，我们分析了不同的CVRF对WMH的影响。作为二次分析，我们观察了年龄和性别差异、萎缩、认知评分和APOE基因型的影响。PET、MRI、FLAIR、人口统计学和心血管健康数据来自阿尔茨海默病神经成像倡议(ADNI-3)(N=287，48%男性)。如果参与者的Florbetapir SUVR和Flortaucipir SUVR分别高于0.79和1.25，则被归类为A+和T+。使用深度卷积神经网络将WMH映射到MRI上(Sepehrband等人，2020)。CVRF评分基于高血压病史、收缩压和舒张压、脉率、呼吸频率、BMI和累积分数，最高分数为6。回归模型和皮尔逊相关性分别被用来检验变量之间的关联和相关性，将年龄、性别、教育年限和扫描仪制造商作为不感兴趣的协变量。WMH体积百分比与整体β-淀粉样蛋白显著相关(r=0.28，p<；0.001)，但与tau无关(r=0.05，p=0.25)。A+或T+病变组WMH体积百分比高于对照组，尤其是A+/T+组(p=0.007，Cohen‘s d=0.4，t=-2.5)。单独的CVRF或累积的CVRF评分与WMH容量增加相关。最后，β淀粉样蛋白与WMH计数最正相关的区域是右侧大脑半球的中颞区(r=0.18p=0.002)和左侧大脑半球的梭形区域(r=0.017，p=0.005)。β-淀粉样蛋白和WMH有明确的联系，尽管促进这种联系的机制仍然不完全清楚。β-淀粉样蛋白与WMH负荷之间的关联强调了β-淀粉样蛋白与血管病变形成之间的关系，而CVRFs、年龄和性别等因素通过不同的机制影响AD的发展。这些发现突出了阿尔茨海默病的潜在原因和机制，作为未来预防和治疗的目标。展望未来，更大的重点可能放在β-淀粉样蛋白的血管效应和AD脑清除受损的影响上。
White matter hyperintensities (WMHs) frequently occur in Alzheimer's Disease (AD) and have a contribution from ischemia, though their relationship with beta-amyloid and cardiovascular risk factors (CVRFs) is not completely understood. We used AT classification to categorize individuals based on their beta-amyloid and tau pathologies, then assessed the effects of beta-amyloid and tau on WMH volume and number. We then determined regions in which beta-amyloid and WMH accumulation were related. Last, we analyzed the effects of various CVRFs on WMHs. As secondary analyses, we observed effects of age and sex differences, atrophy, cognitive scores, and APOE genotype. PET, MRI, FLAIR, demographic, and cardiovascular health data was collected from the Alzheimer's Disease Neuroimaging Initiative (ADNI-3) (N = 287, 48 % male). Participants were categorized as A + and T + if their Florbetapir SUVR and Flortaucipir SUVR were above 0.79 and 1.25, respectively. WMHs were mapped on MRI using a deep convolutional neural network (Sepehrband et al., 2020). CVRF scores were based on history of hypertension, systolic and diastolic blood pressure, pulse rate, respiration rate, BMI, and a cumulative score with 6 being the maximum score. Regression models and Pearson correlations were used to test associations and correlations between variables, respectively, with age, sex, years of education, and scanner manufacturer as covariates of no interest. WMH volume percent was significantly associated with global beta-amyloid (r = 0.28, p < 0.001), but not tau (r = 0.05, p = 0.25). WMH volume percent was higher in individuals with either A + or T + pathology compared to controls, particularly within in the A+/T + group (p = 0.007, Cohen's d = 0.4, t = -2.5). Individual CVRFs nor cumulative CVRF scores were associated with increased WMH volume. Finally, the regions where beta-amyloid and WMH count were most positively associated were the middle temporal region in the right hemisphere (r = 0.18, p = 0.002) and the fusiform region in the left hemisphere (r = 0.017, p = 0.005). beta-amyloid and WMH have a clear association, though the mechanism facilitating this association is still not fully understood. The associations found between beta-amyloid and WMH burden emphasizes the relationship between beta-amyloid and vascular lesion formation while factors like CVRFs, age, and sex affect AD development through various mechanisms. These findings highlight potential causes and mechanisms of AD as targets for future preventions and treatments. Going forward, a larger emphasis may be placed on beta-amyloid's vascular effects and the implications of impaired brain clearance in AD.