Association of candidate genetic variants and circulating levels of ApoE/ApoJ with common neuroimaging features of cerebral amyloid angiopathy
Bonaterra-Pastra, Anna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Benitez, Sonia (Institut d'Investigació Biomèdica Sant Pau)
Pancorbo, Olalla (Hospital Universitari Vall d'Hebron)
Rodriguez-Luna, David (Hospital Universitari Vall d'Hebron)
Vert, Carla (Hospital Universitari Vall d'Hebron)
Rovira, Alex (Hospital Universitari Vall d'Hebron)
Freijo, M. Mar (Instituto de Investigación Sanitaria Biocruces Bizkaia)
Tur, Silvia (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Martínez-Zabaleta, Maite (Hospital de Donostia (Sant Sebastià, País Basc))
Cardona, Pere-Joan (Hospital Universitari de Bellvitge)
Vera, Rocío (Hospital Universitario Ramón y Cajal (Madrid))
Lebrato-Hernández, Lucia (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Arenillas, Juan F. (Universidad de Valladolid)
Pérez-Sánchez, Soledad (Hospital Universitario Virgen Macarena (Sevilla, Andalusia))
Domínguez-Mayoral, Ana (Hospital Universitario Virgen Macarena (Sevilla, Andalusia))
Martí-Fàbregas, Joan (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Mauri, Gerard (Hospital Universitari Arnau de Vilanova)
Montaner, Joan (Hospital Universitario Virgen Macarena (Sevilla, Andalusia))
Sanchez-Quesada, Jose Luis (Institut d'Investigació Biomèdica Sant Pau)
Hernandez Guillamon, Maria Mar (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Data:	2023
Resum:	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. The study was carried out in a multicentric cohort of 126 patients with lobar ICH and clinical suspicion of CAA. 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. 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.
Ajuts:	Instituto de Salud Carlos III PI17/00275 Instituto de Salud Carlos III PI20/00465 Instituto de Salud Carlos III PI20/00334
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	ApoE ; ApoJ ; CAA ; MRI ; Lipoproteins ; EPVS
Publicat a:	Frontiers in aging neuroscience, Vol. 15 (april 2023) , ISSN 1663-4365

DOI: 10.3389/fnagi.2023.1134399
PMID: 37113571

15 p, 2.8 MB

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