Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD.
Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD.
Ann Neurol. 2021 Aug;90(2):227-238. doi: 10.1002/ana.26134. Epub 2021 Jun 5.
Blood-brain barrier (BBB) breakdown has been suggested to be an early biomarker in human cognitive impairment. However, the relationship between BBB breakdown and brain pathology, most commonly Alzheimer disease (AD) and vascular disease, is still poorly understood. The present study measured human BBB function in mild cognitive impairment (MCI) patients on 2 molecular scales, specifically BBB's permeability to water and albumin molecules.
Fifty-five elderly participants were enrolled, including 33 MCI patients and 22 controls. BBB permeability to water was measured with a new magnetic resonance imaging technique, water extraction with phase contrast arterial spin tagging. BBB permeability to albumin was determined using cerebrospinal fluid (CSF)/serum albumin ratio. Cognitive performance was assessed by domain-specific composite scores. AD pathology (including CSF Aβ and ptau) and vascular risk factors were examined.
Compared to cognitively normal subjects, BBB in MCI patients manifested an increased permeability to small molecules such as water but was no more permeable to large molecules such as albumin. BBB permeability to water was found to be related to AD markers of CSF Aβ and ptau. On the other hand, BBB permeability to albumin was found to be related to vascular risk factors, especially hypercholesterolemia, but was not related to AD pathology. BBB permeability to small molecules, but not to large molecules, was found to be predictive of cognitive function.
These findings provide early evidence that BBB breakdown is related to both AD and vascular risks, but their effects can be differentiated by spatial scales. BBB permeability to small molecules has a greater impact on cognitive performance. ANN NEUROL 2021;90:227-238.
血脑屏障（BBB）破坏被认为是人类认知障碍的早期生物标志物。然而，BBB 破坏与脑病理（最常见的是阿尔茨海默病（AD）和血管疾病）之间的关系仍知之甚少。本研究在 2 个分子尺度上测量了轻度认知障碍（MCI）患者的人类 BBB 功能，特别是 BBB 对水和白蛋白分子的通透性。
共纳入 55 名老年参与者，包括 33 名 MCI 患者和 22 名对照。使用新的磁共振成像技术，即相位对比动脉自旋标记水提取法，测量 BBB 对水的通透性。通过脑脊液（CSF）/血清白蛋白比值确定 BBB 对白蛋白的通透性。通过特定领域的综合评分评估认知表现。检查 AD 病理（包括 CSF Aβ 和 ptau）和血管危险因素。
与认知正常的受试者相比，MCI 患者的 BBB 表现出对小分子（如水）的通透性增加，但对大分子（如白蛋白）的通透性没有增加。发现 BBB 对水的通透性与 CSF Aβ 和 ptau 等 AD 标志物有关。另一方面，发现 BBB 对白蛋白的通透性与血管危险因素有关，尤其是高胆固醇血症，但与 AD 病理无关。发现小分子而非大分子的 BBB 通透性与认知功能有关。
这些发现提供了早期证据，表明 BBB 破坏与 AD 和血管风险均有关，但可以通过空间尺度将其影响区分开来。小分子 BBB 通透性对认知表现的影响更大。
