From the Department of Neurology (J.F.S., R.X.S., H.B., C.M.R., S.M., B.A., J.C.M., B.M.A.), Department of Radiology (B.A.G., J.J.C., Y.S., T.L.S.B., B.M.A.), Knight Alzheimer's Disease Research Center (B.A.G., J.C.M., T.L.S.B., B.M.A.), Department of Pathology (J.C.M.), and Hope Center for Neurological Disorders (J.C.M., B.M.A.), Washington University in St. Louis, MO.
Neurology. 2018 Jul 24;91(4):e313-e318. doi: 10.1212/WNL.0000000000005864. Epub 2018 Jun 29.
White matter (WM) projections were assessed from Alzheimer disease (AD) gray matter regions associated with β-amyloid (Aβ), tau, or neurodegeneration to ascertain relationship between WM structural integrity with Aβ and/or tau deposition.
Participants underwent diffusion tensor imaging (DTI), PET Aβ ([F]AV-45 [florbetapir]), and PET tau ([F]AV-1451 [flortaucipir]) imaging. Probabilistic WM summary and individual tracts were created from either a composite or individual gray matter seed regions derived from Aβ, tau, and neurodegeneration. Linear regressions were performed for Aβ, age, tau and WM hyperintensities (WMH) to predict mean diffusivity (MD) or fractional anisotropy (FA) from the corresponding WM summaries or tracts.
Our cohort was composed of 59 cognitively normal participants and 10 cognitively impaired individuals. Aβ was not associated with DTI metrics in WM summary or individual tracts. Age and WMH strongly predicted MD and FA in several WM regions, with tau a significant predictor of MD only in the anterior temporal WM.
Tau, not Aβ, was associated with changes in anterior temporal WM integrity. WMH, a proxy for vascular damage, was strongly associated with axonal damage, but tau independently contributed to the model, suggesting an additional degenerative mechanism within tracts projecting from regions vulnerable to AD pathology. WM decline was associated with early tau accumulation, and further decline may reflect tau propagation in more advanced stages of AD.
从与β-淀粉样蛋白（Aβ）、tau 或神经退行性变相关的阿尔茨海默病（AD）灰质区域评估白质（WM）投射，以确定 WM 结构完整性与 Aβ 和/或 tau 沉积之间的关系。
参与者接受了弥散张量成像（DTI）、PET Aβ（[F]AV-45[florbetapir]）和 PET tau（[F]AV-1451[flortaucipir]）成像。从 Aβ、tau 和神经退行性变的复合或单个灰质种子区域创建 WM 总结和个体束。对 Aβ、年龄、tau 和 WM 高信号（WMH）进行线性回归，以预测相应 WM 总结或束中的平均弥散度（MD）或各向异性分数（FA）。
我们的队列由 59 名认知正常的参与者和 10 名认知受损的个体组成。Aβ 与 WM 总结或个体束中的 DTI 指标无关。年龄和 WMH 强烈预测了几个 WM 区域的 MD 和 FA，tau 仅在前颞 WM 中是 MD 的显著预测因子。
tau 而不是 Aβ 与前颞 WM 完整性的变化有关。WMH，血管损伤的替代物，与轴突损伤强烈相关，但 tau 是该模型的独立预测因子，这表明在从易患 AD 病理的区域投射的束中有额外的退行性机制。WM 下降与早期 tau 积累有关，进一步下降可能反映了 AD 更晚期 tau 的传播。
