Nakaya Moto, Kamagata Koji, Takabayashi Kaito, Andica Christina, Uchida Wataru, Hagiwara Akifumi, Akashi Toshiaki, Wada Akihiko, Taoka Toshiaki, Naganawa Shinji, Abe Osamu, Aoki Shigeki
Department of Radiology, Juntendo University Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
J Cereb Blood Flow Metab. 2025 Mar 13:271678X251321305. doi: 10.1177/0271678X251321305.
The Alzheimer's disease (AD) continuum is characterized by amyloid and tau protein deposition, which is partly attributable to the dysfunction of the brain clearance system. However, the specific phase in the AD continuum wherein aberrant clearance is present remains unclear. This study aimed to assess noninvasive magnetic resonance imaging (MRI) indices related to brain clearance functions, such as choroid plexus volume (CPV), lateral ventricular volume (LVV), and the index of diffusivity along the perivascular space (ALPS index), across the Alzheimer's disease (AD) spectrum. The CPV, LVV, and ALPS index in amyloid beta (Aβ)-negative healthy controls (HCs) and Aβ-positive HCs as well as in patients with Aβ-negative subjective cognitive decline (SCD), with Aβ-positive SCD, with mild cognitive impairment, and with AD were evaluated. The CPV and LVV were higher, whereas the ALPS index was lower in the patients with more severe disease. The ALPS index was significantly lower in Aβ-positive HCs than in Aβ-negative HCs. In SCD patients and those in the AD continuum, the MRI-based clearance markers were correlated with P-tau and T-tau protein levels and cognitive scores. In summary, brain clearance markers on MRI are associated with tau deposition, neurodegeneration and cognitive dysfunction.
阿尔茨海默病（AD）连续体的特征是淀粉样蛋白和tau蛋白沉积，这部分归因于脑清除系统功能障碍。然而，AD连续体中存在异常清除的具体阶段仍不清楚。本研究旨在评估与脑清除功能相关的非侵入性磁共振成像（MRI）指标，如脉络丛体积（CPV）、侧脑室体积（LVV）以及沿血管周围间隙的扩散指数（ALPS指数），涵盖阿尔茨海默病（AD）谱系。评估了淀粉样β（Aβ）阴性健康对照（HCs）、Aβ阳性HCs以及Aβ阴性主观认知下降（SCD）患者、Aβ阳性SCD患者、轻度认知障碍患者和AD患者的CPV、LVV和ALPS指数。病情越严重的患者，CPV和LVV越高，而ALPS指数越低。Aβ阳性HCs的ALPS指数显著低于Aβ阴性HCs。在SCD患者和AD连续体患者中，基于MRI的清除标志物与磷酸化tau蛋白（P-tau）和总tau蛋白（T-tau）水平以及认知评分相关。总之，MRI上的脑清除标志物与tau沉积、神经退行性变和认知功能障碍有关。
