School of Computing and Augmented Intelligence, Arizona State University, Tempe, AZ, USA.
Banner Alzheimer's Institute, Phoenix, AZ, USA.
J Alzheimers Dis. 2023;93(3):1153-1168. doi: 10.3233/JAD-230034.
Alzheimer's disease (AD) is the most common type of age-related dementia, affecting 6.2 million people aged 65 or older according to CDC data. It is commonly agreed that discovering an effective AD diagnosis biomarker could have enormous public health benefits, potentially preventing or delaying up to 40% of dementia cases. Tau neurofibrillary tangles are the primary driver of downstream neurodegeneration and subsequent cognitive impairment in AD, resulting in structural deformations such as hippocampal atrophy that can be observed in magnetic resonance imaging (MRI) scans.
To build a surface-based model to 1) detect differences between APOE subgroups in patterns of tau deposition and hippocampal atrophy, and 2) use the extracted surface-based features to predict cognitive decline.
Using data obtained from different institutions, we develop a surface-based federated Chow test model to study the synergistic effects of APOE, a previously reported significant risk factor of AD, and tau on hippocampal surface morphometry.
We illustrate that the APOE-specific morphometry features correlate with AD progression and better predict future AD conversion than other MRI biomarkers. For example, a strong association between atrophy and abnormal tau was identified in hippocampal subregion cornu ammonis 1 (CA1 subfield) and subiculum in e4 homozygote cohort.
Our model allows for identifying MRI biomarkers for AD and cognitive decline prediction and may uncover a corner of the neural mechanism of the influence of APOE and tau deposition on hippocampal morphology.
根据美国疾病控制与预防中心的数据，阿尔茨海默病（AD）是最常见的与年龄相关的痴呆症类型，影响着 65 岁及以上的 620 万人。人们普遍认为，发现有效的 AD 诊断生物标志物将具有巨大的公共卫生效益，有可能预防或延缓多达 40%的痴呆病例。Tau 神经原纤维缠结是 AD 下游神经退行性变和随后认知障碍的主要驱动因素，导致磁共振成像（MRI）扫描中可观察到的结构变形，如海马体萎缩。
建立基于表面的模型，以 1）检测 APOE 亚组中 Tau 沉积和海马体萎缩模式的差异，2）使用提取的基于表面的特征来预测认知能力下降。
利用来自不同机构的数据，我们开发了一个基于表面的联合 Chow 测试模型，以研究 APOE（AD 的一个先前报道的显著风险因素）和 Tau 对海马体表面形态的协同作用。
我们表明，APOE 特异性形态特征与 AD 进展相关，并且比其他 MRI 生物标志物更好地预测未来的 AD 转化。例如，在 e4 纯合子队列中，CA1 亚区和海马旁回的萎缩与异常 Tau 之间存在强烈的相关性。
我们的模型可以识别 AD 和认知能力下降的 MRI 生物标志物，并可能揭示 APOE 和 Tau 沉积对海马体形态影响的神经机制的一个角落。
