Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA.
Neurobiol Aging. 2021 Jun;102:111-118. doi: 10.1016/j.neurobiolaging.2021.02.003. Epub 2021 Feb 10.
Alzheimer's disease (AD) is associated with reduced temporo-parietal cerebral blood flow (CBF). However, a substantial variability in CBF across the clinical spectrum of AD has been reported, possibly due to differences in primary AD pathologies. Here, we assessed CBF (ASL-MRI), tau (AV1451-PET) and amyloid (AV45/FBB-PET) in 156 subjects across the AD continuum. Using mixed-effect regression analyses, we assessed the local associations between amyloid-PET, tau-PET and CBF in a hypothesis-driven way focusing on each pathology's predilection areas. The contribution of Apolipoprotein E (APOE) genotype, and MRI markers of small vessel disease (SVD) to alterations in CBF were assessed as well. Tau-PET was associated with lower CBF in the entorhinal cortex, independent of Aβ. Amyloid-PET was associated with lower CBF in temporo-parietal regions. No associations between MRI markers of SVD and CBF were observed. These results provide evidence that in addition to Aβ, pathologic tau is a major correlate of CBF in early Braak stages, independent of Aβ, APOE genotype and SVD markers.
阿尔茨海默病（AD）与颞顶叶脑血流（CBF）减少有关。然而，据报道，AD 临床谱中 CBF 的变化很大，这可能是由于主要 AD 病理的差异。在这里，我们评估了 156 名 AD 连续体患者的 CBF（ASL-MRI）、tau（AV1451-PET）和淀粉样蛋白（AV45/FBB-PET）。使用混合效应回归分析，我们以假设驱动的方式评估了淀粉样蛋白-PET、tau-PET 和 CBF 之间的局部关联，重点关注每种病理的倾向区域。还评估了载脂蛋白 E（APOE）基因型和小血管疾病（SVD）的 MRI 标志物对 CBF 改变的影响。tau-PET 与内侧颞叶皮层的 CBF 降低有关，与 Aβ 无关。淀粉样蛋白-PET 与颞顶叶区域的 CBF 降低有关。SVD 的 MRI 标志物与 CBF 之间没有关联。这些结果提供了证据，表明除了 Aβ，病理性 tau 是早期 Braak 阶段 CBF 的主要相关物，与 Aβ、APOE 基因型和 SVD 标志物无关。
