血脑屏障的完整性影响了血浆淀粉样蛋白-β作为脑淀粉样蛋白-β病理学替代物的应用。
Blood-brain barrier integrity impacts the use of plasma amyloid-β as a proxy of brain amyloid-β pathology.
机构信息
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
出版信息
Alzheimers Dement. 2023 Sep;19(9):3815-3825. doi: 10.1002/alz.13014. Epub 2023 Mar 15.
INTRODUCTION
Amyloid-β (Aβ) and tau can be quantified in blood. However, biological factors can influence the levels of brain-derived proteins in the blood. The blood-brain barrier (BBB) regulates protein transport between cerebrospinal fluid (CSF) and blood. BBB altered permeability might affect the relationship between brain and blood biomarkers.
METHODS
We assessed 224 participants in research (TRIAD, n = 96) and clinical (BIODEGMAR, n = 128) cohorts with plasma and CSF/positron emission tomography Aβ, p-tau, and albumin measures.
RESULTS
Plasma Aβ better identified CSF Aβ and Aβ-PET positivity in individuals with high BBB permeability. An interaction between plasma Aβ and BBB permeability on CSF Aβ was observed. Voxel-wise models estimated that the association of positron emission tomography (PET), with plasma Aβ was most affected by BBB permeability in AD-related brain regions. BBB permeability did not significantly impact the relationship between brain and plasma p-tau levels.
DISCUSSION
These findings suggest that BBB integrity may influence the performance of plasma Aβ, but not p-tau, biomarkers in research and clinical settings.
HIGHLIGHTS
BBB permeability affects the association between brain and plasma Aβ levels. BBB integrity does not affect the association between brain and plasma p-tau levels. Plasma Aβ was most affected by BBB permeability in AD-related brain regions. BBB permeability increases with age but not according to cognitive status.
简介
淀粉样蛋白-β（Aβ）和 tau 可在血液中定量。然而，生物因素会影响血液中脑源性蛋白的水平。血脑屏障（BBB）调节脑脊液（CSF）和血液之间的蛋白质转运。BBB 通透性改变可能会影响脑与血生物标志物之间的关系。
方法
我们评估了研究（TRIAD，n=96）和临床（BIODEGMAR，n=128）队列中的 224 名参与者的血浆和 CSF/正电子发射断层扫描 Aβ、p-tau 和白蛋白水平。
结果
在 BBB 通透性高的个体中，血浆 Aβ 能更好地识别 CSF Aβ 和 Aβ-PET 阳性。观察到血浆 Aβ 和 BBB 通透性对 CSF Aβ 的相互作用。体素模型估计，正电子发射断层扫描（PET）与血浆 Aβ 的相关性受 AD 相关脑区 BBB 通透性的影响最大。BBB 通透性对脑与血浆 p-tau 水平之间的关系没有显著影响。
讨论
这些发现表明，BBB 完整性可能会影响研究和临床环境中血浆 Aβ 而不是 p-tau 生物标志物的性能。
重点
BBB 通透性会影响大脑和血浆 Aβ 水平之间的关联。BBB 完整性不影响大脑和血浆 p-tau 水平之间的关联。AD 相关脑区的 BBB 通透性对血浆 Aβ 的影响最大。BBB 通透性随年龄增加而增加，但与认知状态无关。
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