PURPOSE Recent evidence suggests that PET imaging with amyloid-β (Aβ) tracers can be used to assess myelin integrity in cerebral white matter (WM). Alzheimer's disease (AD) is characterized by myelin changes that are believed to occur early in the disease course. Nevertheless, the extent to which demyelination, as measured with Aβ PET, contributes to AD progression remains unexplored. METHODS Participants with concurrent 18F-florbetapir (FBP) PET, MRI, and cerebrospinal fluid (CSF) examinations were included (241 cognitively normal, 347 Aβ-positive cognitively impaired, and 207 Aβ-negative cognitively impaired subjects). A subset of these participants had also available diffusion tensor imaging (DTI) images (n = 195). We investigated cross-sectional associations of FBP retention in the white matter (WM) with MRI-based markers of WM degeneration, AD clinical progression, and fluid biomarkers. In longitudinal analyses, we used linear mixed models to assess whether FBP retention in normal-appearing WM (NAWM) predicted progression of WM hyperintensity (WMH) burden and clinical decline. RESULTS In AD-continuum individuals, FBP retention in NAWM was (1) higher compared with WMH regions, (2) associated with DTI-based measures of WM integrity, and (3) associated with longitudinal progression of WMH burden. FBP uptake in WM decreased across the AD continuum and with increasingly abnormal CSF biomarkers of AD. Furthermore, FBP retention in the WM was associated with large-calibre axon degeneration as reflected by abnormal plasma neurofilament light chain levels. Low FBP uptake in NAWM predicted clinical decline in preclinical and prodromal AD, independent of demographics, global cortical Aβ, and WMH burden. Most of these associations were also observed in Aβ-negative cognitively impaired individuals. CONCLUSION These results support the hypothesis that FBP retention in the WM is myelin-related. Demyelination levels progressed across the AD continuum and were associated with clinical progression at early stages, suggesting that this pathologic process might be a relevant degenerative feature in the disease course.

中文翻译：

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18F-florbetapir PET 作为阿尔茨海默病谱中髓鞘完整性的标志物。

目的 最近的证据表明，使用淀粉样蛋白-β (Aβ) 示踪剂的 PET 成像可用于评估脑白质 (WM) 中的髓鞘完整性。阿尔茨海默病 (AD) 的特征在于被认为发生在病程早期的髓鞘变化。然而，用 Aβ PET 测量的脱髓鞘对 AD 进展的影响程度仍未得到探索。方法 纳入同时进行 18F-florbetapir (FBP) PET、MRI 和脑脊液 (CSF) 检查的参与者（241 名认知正常、347 名 Aβ 阳性认知受损和 207 名 Aβ 阴性认知受损受试者）。这些参与者的一个子集也有可用的扩散张量成像 (DTI) 图像 (n = 195)。我们调查了白质 (WM) 中 FBP 保留与基于 MRI 的 WM 变性标志物、AD 临床进展和液体生物标志物的横断面关联。在纵向分析中，我们使用线性混合模型来评估 FBP 在正常出现的 WM (NAWM) 中的保留是否可以预测 WM 高信号 (WMH) 负担的进展和临床下降。结果 在 AD-continuum 个体中，NAWM 中的 FBP 保留率 (1) 高于 WMH 区域，(2) 与基于 DTI 的 WM 完整性测量相关，(3) 与 WMH 负担的纵向进展相关。WM 中的 FBP 摄取在整个 AD 连续体中下降，并且随着 AD 的 CSF 生物标志物异常增加。此外，如异常血浆神经丝轻链水平所反映的，WM 中的 FBP 保留与大口径轴突变性有关。NAWM 中的低 FBP 摄取预示着临床前和前驱期 AD 的临床下降，与人口统计学、全球皮质 Aβ 和 WMH 负担无关。在 Aβ 阴性认知障碍个体中也观察到大多数这些关联。结论 这些结果支持 WM 中 FBP 保留与髓磷脂相关的假设。脱髓鞘水平在整个 AD 连续体中进展，并与早期临床进展相关，这表明这种病理过程可能是疾病过程中相关的退行性特征。结论 这些结果支持 WM 中 FBP 保留与髓磷脂相关的假设。脱髓鞘水平在整个 AD 连续体中进展，并与早期临床进展相关，这表明这种病理过程可能是疾病过程中相关的退行性特征。结论 这些结果支持 WM 中 FBP 保留与髓磷脂相关的假设。脱髓鞘水平在整个 AD 连续体中进展，并与早期临床进展相关，这表明这种病理过程可能是疾病过程中相关的退行性特征。