Comparison of Plasma Lipoprotein Composition and Function in Cerebral Amyloid Angiopathy and Alzheimer’s Disease

Malaltia d'Alzheimer; Apolipoproteïnes; Angiopatia amiloide cerebralEnfermedad de Alzheimer; Apolipoproteínas; Angiopatía amiloide cerebralAlzheimer’s disease; Apolipoproteins; Cerebral amyloid angiopathyCerebral amyloid angiopathy (CAA) refers to beta-amyloid (Aβ) deposition in brain vessels and is clinically the main cause of lobar intracerebral hemorrhage (ICH). Aβ can also accumulate in brain parenchyma forming neuritic plaques in Alzheimer’s disease (AD). Our study aimed to determine whether the peripheral lipid profile and lipoprotein composition are associated with cerebral beta-amyloidosis pathology and may reflect biological differences in AD and CAA. For this purpose, lipid and apolipoproteins levels were analyzed in plasma from 51 ICH-CAA patients (collected during the chronic phase of the disease), 60 AD patients, and 60 control subjects. Lipoproteins (VLDL, LDL, and HDL) were isolated and their composition and pro/antioxidant ability were determined. We observed that alterations in the lipid profile and lipoprotein composition were remarkable in the ICH-CAA group compared to control subjects, whereas the AD group presented no specific alterations compared with controls. ICH-CAA patients presented an atheroprotective profile, which consisted of lower total and LDL cholesterol levels. Plasma from chronic ICH-CAA patients also showed a redistribution of ApoC-III from HDL to VLDL and a higher ApoE/ApoC-III ratio in HDL. Whether these alterations reflect a protective response or have a causative effect on the pathology requires further investigation.This research was funded by Instituto de Salud Carlos III (co-financed by the European Regional Development Fund FEDER “Una manera de hacer Europa”), grant numbers PI13/00364, PI16/00471, PI14/01134 and PI17/00275. A.R.-U. was funded by Instituto de Salud Carlos III predoctoral contract FI17/00031. The Neurovascular Research Laboratory is part of the INVICTUS+ network, ISCIII, Spain [RD16/0019/0021]. J.L.S.-Q. is a member of the CIBER of Diabetes and Metabolism (CIBERDEM), ISCIII, Spain. M.H.-G. is supported by the Miguel Servet programme, ISCIII, Spain [CPII17/00010]. A.R.-U., N.P., S.B. and J.L.S.-Q. are members of the Quality Research Group 2017-SGR-1149 from Generalitat de Catalunya. A.R.-U., N.P., S.B. and J.L.S.-Q. are members of the Group of Vascular Biology from the Spanish Atherosclerosis Society