Reas Emilie T, Solders Seraphina K, Tsiknia Amaryllis, Triebswetter Curtis, Shen Qian, Rivera Charlotte S, Andrews Murray J, Alderson-Myers Austin, Brewer James B
Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Marina Del Rey, California, USA.
Alzheimers Dement. 2024 Dec;20(12):8615-8624. doi: 10.1002/alz.14302. Epub 2024 Oct 16.
Blood-brain barrier (BBB) dysfunction occurs in Alzheimer's disease (AD). Yet, the stage at which it appears along the AD time course and whether it contributes to neurodegeneration remain unclear.
Older adults (61 to 90 years) from cognitively normal (CN) to mildly cognitively impaired (CI), enriched for APOE 𝜀4 and amyloid positivity, underwent dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and diffusion MRI to measure BBB permeability and brain microstructure. Analysis of variance compared BBB permeability according to cognitive status, amyloid beta (Aβ), and APOE4. Linear regressions assessed associations of BBB permeability with brain microstructure and interactions with Aβ and APOE4.
BBB permeability was elevated for APOE4 carriers across the cortical gray matter, with the strongest differences among CN amyloid-negative individuals. Associations between entorhinal BBB permeability and microstructure interacted with Aβ and APOE4, with the strongest relationships in amyloid-positive individuals and APOE4 carriers.
APOE4 may drive widespread BBB dysfunction in preclinical AD, which may contribute to neurodegenerative changes early along the AD cascade.
Gray matter blood-brain barrier (BBB) permeability is elevated for APOE4 carriers. APOE4-related BBB breakdown appears in the absence of cognitive decline or amyloid. BBB leakage correlates with entorhinal cortex microstructural injury. Associations with microstructure are strongest for amyloid-positive APOE4 carriers.
血脑屏障（BBB）功能障碍在阿尔茨海默病（AD）中会出现。然而，其在AD病程中出现的阶段以及是否会导致神经退行性变仍不清楚。
纳入年龄在61至90岁之间、从认知正常（CN）到轻度认知障碍（CI）、富含APOE ε4且淀粉样蛋白呈阳性的老年人，进行动态对比增强（DCE）磁共振成像（MRI）和扩散MRI，以测量BBB通透性和脑微结构。方差分析根据认知状态、淀粉样β蛋白（Aβ）和APOE4比较BBB通透性。线性回归评估BBB通透性与脑微结构的关联以及与Aβ和APOE4的相互作用。
APOE4携带者的整个皮质灰质BBB通透性升高，在CN淀粉样蛋白阴性个体中差异最为显著。内嗅区BBB通透性与微结构之间的关联与Aβ和APOE4相互作用，在淀粉样蛋白阳性个体和APOE4携带者中关系最为密切。
APOE4可能在临床前AD中导致广泛的BBB功能障碍，这可能在AD级联反应早期促成神经退行性变化。
APOE4携带者的灰质血脑屏障（BBB）通透性升高。APOE4相关的BBB破坏在无认知衰退或淀粉样蛋白的情况下出现。BBB渗漏与内嗅皮质微结构损伤相关。对于淀粉样蛋白阳性的APOE4携带者，与微结构的关联最为强烈。
