Heston Margo B, Teague Jordan P, Cody Karly A, Deming Yuetiva, Ruiz de Chavez Elena, Morse Jacob, Chin Nathaniel A, Engelman Corinne D, Chappell Richard J, Langhough Rebecca E, Gleason Carey E, Clark Lindsay R, Zuelsdorff Megan L, Betthauser Tobey J
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Alzheimers Dement. 2025 Aug;21(8):e70551. doi: 10.1002/alz.70551.
Elevated tau (T+) is temporally proximal to dementia onset but less is known about factors influencing T+ onset age and time to dementia after T+ in Alzheimer's disease (AD). We used sampled iterative local approximation (SILA) estimated T+ onset age (ETOA) to investigate factors associated with T+ age and time from T+ to dementia onset in the Alzheimer's Disease Neuroimaging Initiative.
Using SILA-estimated amyloid positivity and T+ onset ages derived from F-Flortaucipir, F-Florbetapir, and F-Florbetaben positron emission tomography and Cox proportional hazards and accelerated failure time models, we analyzed apolipoprotein E (APOE), sex, amyloid burden, age, educational attainment, and literacy associations with ETOA and time from T+ to dementia.
Higher amyloid, APOE-ε4, lower education, and lower literacy associated with younger ETOA. Older ETOA and higher amyloid associated with shorter time from T+ to dementia.
This work highlights the prognostic value of ETOA and the need to better characterize factors contributing to ETOA and dementia onset in AD.
We applied sampled iterative local approximation (SILA) to Alzheimer's Disease Neuroimaging Initiative F-Flortaucipir data, to estimate individuals' age of tau pathology onset (T+) and time from T+ onset to dementia. Higher amyloid, apolipoprotein E ε4, lower education, and lower literacy associated with younger estimated T+ onset age. Older T+ onset age and higher amyloid associated with shorter time from T+ to dementia. Only one individual was observed to remain dementia free 14 years after T+ onset. This work highlights the prognostic value of T+ onset age and the need to better characterize factors contributing to T+ onset age and dementia onset in Alzheimer's disease.
tau升高（T+）在时间上与痴呆症发病临近，但对于阿尔茨海默病（AD）中影响T+发病年龄以及T+后至痴呆症发病时间的因素，我们了解得较少。我们使用抽样迭代局部近似法（SILA）估计T+发病年龄（ETOA），以研究阿尔茨海默病神经影像倡议（ADNI）中与T+年龄以及从T+到痴呆症发病时间相关的因素。
利用从氟代tau蛋白显像剂F-Flortaucipir、氟代贝他匹F-Florbetapir和氟代贝他班F-Florbetaben正电子发射断层扫描得出的SILA估计的淀粉样蛋白阳性结果和T+发病年龄，以及Cox比例风险模型和加速失效时间模型，我们分析了载脂蛋白E（APOE）、性别、淀粉样蛋白负荷、年龄、受教育程度和读写能力与ETOA以及从T+到痴呆症的时间之间的关联。
较高的淀粉样蛋白、APOE-ε4、较低的教育程度和较低的读写能力与较年轻的ETOA相关。较老的ETOA和较高的淀粉样蛋白与从T+到痴呆症的较短时间相关。
这项工作突出了ETOA的预后价值，以及更好地描述导致AD中ETOA和痴呆症发病的因素的必要性。
我们将抽样迭代局部近似法（SILA）应用于阿尔茨海默病神经影像倡议（ADNI）的氟代tau蛋白显像剂F-Flortaucipir数据，以估计个体的tau病理发病年龄（T+）以及从T+发病到痴呆症的时间。较高的淀粉样蛋白、载脂蛋白E ε4、较低的教育程度和较低的读写能力与较年轻的估计T+发病年龄相关。较老的T+发病年龄和较高的淀粉样蛋白与从T+到痴呆症的较短时间相关。仅观察到一名个体在T+发病14年后仍未患痴呆症。这项工作突出了T+发病年龄的预后价值，以及更好地描述导致阿尔茨海默病中T+发病年龄和痴呆症发病的因素的必要性。
