■脑淀粉样血管病(CAA)的特征是淀粉样蛋白-β(Aβ)在脑血管中的积累,是老年人大叶脑出血(ICH)的主要原因。CAA与小血管疾病(SVD)的磁共振成像(MRI)标记相关。由于Aβ也在阿尔茨海默病(AD)的脑实质中积累,我们的目的是研究先前与AD相关的几个单核苷酸多态性(SNPs)是否也与CAA病理学相关.此外,我们还研究了APOE和CLU遗传变异对载脂蛋白E(ApoE)和簇蛋白/载脂蛋白J(ApoJ)循环水平的影响及其在脂蛋白中的分布.
■这项研究是在126例叶脑出血和临床怀疑CAA患者的多中心队列中进行的。
■我们观察到一些与CAA神经影像学MRI标记相关的SNP[皮质浅表铁质沉着症(cSS),半卵中心血管周围空间扩大(CSO-EPVS),脑叶微出血(CMB),白质高强度(WMH),皮质下皮质萎缩和CAA-SVD负荷评分]。具体而言,ABCA7(rs3764650),CLU(rs9331896和rs933188),EPHA1(rs11767557),和TREML2(rs3747742)与CAA-SVD负荷评分显著相关。关于载脂蛋白的循环水平,CLU的保护性ADSNP[rs11136000(T)和rs9331896(C)]与脑叶ICH队列中较高的HDLApoJ含量显著相关.AP0Eε2携带者呈现较高的血浆和LDL相关的ApoE水平,而AP0Eε4携带者呈现较低的血浆ApoE水平。此外,我们观察到较低的循环ApoJ和ApoE水平与CAA相关的MRI标志物显著相关.更具体地说,较低的LDL相关ApoJ和血浆和HDL相关ApoE水平与CSO-EPVS显著相关,随着cSS程度的增加,HDL中ApoJ含量降低,LDL中ApoE含量降低。
■这项研究加强了CAA中脂质代谢与脑血管功能的相关性。我们认为ApoJ和ApoE在脂蛋白中的分布可能与与HDL中较高的ApoE和ApoJ水平的CAA相关的病理特征有关,可能会增强动脉粥样硬化保护作用。抗氧化,脑β-淀粉样变性中的抗炎反应。
UNASSIGNED: Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid-β (Aβ) in brain vessels and is a main cause of lobar intracerebral hemorrhage (ICH) in the elderly. CAA is associated with magnetic resonance imaging (MRI) markers of small vessel disease (SVD). Since Aβ is also accumulated in Alzheimer\'s disease (AD) in the brain parenchyma, we aimed to study if several single nucleotide polymorphisms (SNPs) previously associated with AD were also associated with CAA pathology. Furthermore, we also studied the influence of APOE and CLU genetic variants in apolipoprotein E (ApoE) and clusterin/apolipoprotein J (
ApoJ) circulating levels and their distribution among lipoproteins.
UNASSIGNED: The study was carried out in a multicentric cohort of 126 patients with lobar ICH and clinical suspicion of CAA.
UNASSIGNED: We observed several SNPs associated with CAA neuroimaging MRI markers [cortical superficial siderosis (cSS), enlarged perivascular spaces in the centrum semiovale (CSO-EPVS), lobar cerebral microbleeds (CMB), white matter hyperintensities (WMH), corticosubcortical atrophy and CAA-SVD burden score]. Concretely, ABCA7 (rs3764650), CLU (rs9331896 and rs933188), EPHA1 (rs11767557), and TREML2 (rs3747742) were significantly associated with a CAA-SVD burden score. Regarding circulating levels of apolipoproteins, protective AD SNPs of CLU [rs11136000 (T) and rs9331896 (C)] were significantly associated with higher HDL ApoJ content in the lobar ICH cohort. APOEε2 carriers presented higher plasma and LDL-associated ApoE levels whereas APOEε4 carriers presented lower plasma ApoE levels. Additionally, we observed that lower circulating
ApoJ and ApoE levels were significantly associated with CAA-related MRI markers. More specifically, lower LDL-associated
ApoJ and plasma and HDL-associated ApoE levels were significantly associated with CSO-EPVS, lower
ApoJ content in HDL with brain atrophy and lower ApoE content in LDL with the extent of cSS.
UNASSIGNED: This study reinforces the relevance of lipid metabolism in CAA and cerebrovascular functionality. We propose that
ApoJ and ApoE distribution among lipoproteins may be associated with pathological features related to CAA with higher ApoE and ApoJ levels in HDL possibly enhancing atheroprotective, antioxidative, and anti-inflammatory responses in cerebral β-amyloidosis.