Kettunen Petronella, Bjerke Maria, Eckerström Carl, Jonsson Michael, Zetterberg Henrik, Blennow Kaj, Svensson Johan, Wallin Anders
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy University of Gothenburg Gothenburg Sweden.
Laboratory of Neurochemistry, Department of Clinical Biology and Center for Neurosciences Universitair Ziekenhuis Brussel Brussels Belgium.
Alzheimers Dement (Amst). 2022 Mar 25;14(1):e12296. doi: 10.1002/dad2.12296. eCollection 2022.
Subcortical small-vessel disease (SSVD) is the most common vascular cognitive disorder. However, because no disease-specific cerebrospinal fluid (CSF) biomarkers are available for SSVD, our aim was to identify such markers.
We included 170 healthy controls and patients from the Gothenburg Mild Cognitive Impairment (MCI) study clinically diagnosed with SSVD dementia, Alzheimer's disease (AD), or mixed AD/SSVD. We quantified CSF levels of amyloid-β (Aβ), Aβ, Aβ, as well as soluble amyloid precursor protein (sAPP)-α and sAPP-β.
sAPP-β was lower in SSVD patients than in AD patients and controls. Receiver-operating characteristic (ROC) analyses showed that sAPP-β moderately separated SSVD from AD and controls. Moreover, the CSF/serum albumin ratio was elevated exclusively in SSVD and could moderately separate SSVD from the other groups in ROC analyses.
SSVD has a biomarker profile that differs from that of AD and controls, and to some extent also from mixed AD/SSVD, suggesting that signs of blood-brain barrier (BBB) dysfunction and sAPP-β could be additional tools to diagnose SSVD.
Patients with subcortical small-vessel disease (SSVD) exhibited reduced levels of sAPP-β and disturbances of the blood-brain barrier (BBB).This biochemical pattern is different from that of Alzheimer's disease (AD) and to some degree from that of mixed AD/SSVD.Our findings are speaking in favor of the concept that SSVD is a distinct vascular cognitive disorder (VCD) form.
皮质下小血管病（SSVD）是最常见的血管性认知障碍。然而，由于目前尚无针对SSVD的疾病特异性脑脊液（CSF）生物标志物，我们的目的是识别此类标志物。
我们纳入了170名健康对照者以及来自哥德堡轻度认知障碍（MCI）研究的患者，这些患者临床上被诊断为SSVD痴呆、阿尔茨海默病（AD）或AD/SSVD混合型。我们对脑脊液中淀粉样蛋白β（Aβ）、Aβ、Aβ以及可溶性淀粉样前体蛋白（sAPP）-α和sAPP-β的水平进行了定量分析。
SSVD患者的sAPP-β水平低于AD患者和对照者。受试者工作特征（ROC）分析表明，sAPP-β能在一定程度上区分SSVD与AD及对照者。此外，仅在SSVD患者中脑脊液/血清白蛋白比值升高，在ROC分析中该比值能在一定程度上区分SSVD与其他组。
SSVD具有与AD及对照者不同的生物标志物特征，在一定程度上也与AD/SSVD混合型不同，这表明血脑屏障（BBB）功能障碍的迹象和sAPP-β可能是诊断SSVD的额外工具。
皮质下小血管病（SSVD）患者表现出sAPP-β水平降低和血脑屏障（BBB）紊乱。这种生化模式不同于阿尔茨海默病（AD），在一定程度上也不同于AD/SSVD混合型。我们的研究结果支持SSVD是一种独特的血管性认知障碍（VCD）形式这一概念。
