title: ApoA1, ApoJ and ApoE Plasma Levels and Genotype Frequencies in Cerebral Amyloid Angiopathy.
abstract: The involvement of apolipoproteins, such as the ApoE4 isoform, in Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) highlights the fact that certain lipid carriers may participate in soluble β-amyloid (Aβ) transport. Our general aim was to characterize the soluble levels of the apolipoproteins apoE, apoA1 and apoJ/clusterin and their genotype status in patients with CAA. We analyzed the genotypes frequency of APOA1 (rs5069, rs670), CLU (rs11136000, rs1532278, rs7012010, rs9331888) and APOE (rs429358, rs7412) in a cohort of patients with CAA-associated intracerebral hemorrhage (ICH) (n = 59) and compared the results with those from hypertension-associated ICH (n = 42), AD patients (n = 73) and controls (n = 88). In a subgroup of patients, we also determined the plasma concentrations of apoE, apoA1 and apoJ/clusterin. We found increased plasma apoJ/clusterin levels in CAA patients compared to AD patients or controls after adjusting for sex and age (CAA vs. controls, p = 0.033; CAA vs. AD, p = 0.013). ApoA1 levels were not altered between groups, although a strong correlation was observed between plasma Aβ(1-40) and apoA1 among CAA patients (r = 0.583, p = 0.007). Regarding plasma apoE concentration, a robust association between circulating levels and genotype status was confirmed (p < 0.001). Whereas the APOE4 frequency was higher in AD (p < 0.001) and CAA (p = 0.013), the APOA1 and CLU genotypes were not different among groups. In the CAA cohort, the risk-linked CLU variant (C) rs11136000 was associated with white matter hyperintensities (p = 0.045) and the presence of lobar microbleeds (p = 0.023) on MRI. In summary, our findings suggest that apoA1 may act as a physiological transporter of Aβ(1-40) and that apoJ/clusterin appears to be a chaperone related to distinctive lesions in CAA brains.
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain.
authors.forename: Alex
authors.initials: A
authors.lastname: Montañola
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain.
authors.forename: Sofía Fernández
authors.initials: SF
authors.lastname: de Retana
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Rueda
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Merino-Zamorano
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Penalba
authors.affiliation: Department of Clinical and Molecular Genetics, Vall d'Hebron Hospital, Barcelona, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Fernández-Álvarez
authors.affiliation: Neurovascular Unit, Neurology Department, Vall d'Hebron Hospital, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Rodríguez-Luna
authors.affiliation: Dementia Unit, Neurology Department, Vall d'Hebron Hospital, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Malagelada
authors.affiliation: Dementia Unit, Neurology Department, Vall d'Hebron Hospital, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Pujadas
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain.|Neurovascular Unit, Neurology Department, Vall d'Hebron Hospital, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain. mar.hernandez.guillamon@vhir.org.
authors.forename: Mar
authors.initials: M
authors.lastname: Hernández-Guillamon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics*; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D016657:Cerebral Amyloid Angiopathy / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D028243:Cerebral Amyloid Angiopathy, Familial / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics; D002543:Cerebral Hemorrhage / Q000209:etiology; D051152:Clusterin / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D066127:White Matter / Q000473:pathology
chemical_list: C505693:APOA1 protein, human; C000612345:ApoE protein, human; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; C495242:CLU protein, human; D051152:Clusterin
keywords: APOA1; APOE; APOJ; Alzheimer’s disease; CLU; Cerebral Amyloid Angiopathy; Clusterin; apoA1; apoE; apoJ