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Title: Association of candidate genetic variants and circulating levels of ApoE/ApoJ with common neuroimaging features of cerebral amyloid angiopathy
Author: Bonaterra Pastra, Anna
Benítez, Sònia
Pancorbo, Olalla
Rodríguez Luna, David
Vert, Carla
Rovira, Alex
Freijo, Maria del Mar
Tur, Silvia
Martínez Zabaleta, Maite
Cardona Portela, Pere
Vera, Rocío
Lebrato Hernández, Lucia
Arenillas, Juan F.
Pérez Sánchez, Soledad
Domínguez Mayoral, Ana
Martí Fàbregas, Joan
Mauri, Gerard
Montaner, Joan
Sánchez Quesada, Jose Luis
Hernández Guillamon, Mar
Keywords: Malalties del sistema nerviós central
Vasos sanguinis
Imatges per ressonància magnètica
Central nervous system diseases
Blood vessels
Magnetic resonance imaging
Issue Date: 11-Apr-2023
Publisher: Frontiers Media
Abstract: IntroductionCerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid-beta (A beta) 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 A beta 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. MethodsThe study was carried out in a multicentric cohort of 126 patients with lobar ICH and clinical suspicion of CAA. ResultsWe 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. APOE epsilon 2 carriers presented higher plasma and LDL-associated ApoE levels whereas APOE epsilon 4 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. DiscussionThis 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 beta-amyloidosis.
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It is part of: Frontiers in Aging Neuroscience, 2023, vol. 15
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ISSN: 1663-4365
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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