Plasma lipoprotein β-amyloid in subjects with Alzheimer's disease or mild cognitive impairment

Background: Plasma amyloid p-peptide (Ap) can compromise the blood-brain barrier, contributing to cerebrovascular alterations and amyloid angiopathy in Alzheimer's disease (AD). The objectives of this study were to investigate the distribution of lipoprotein-bound plasma-Aβ isoforms. Methods: This involved a case-control study of subjects with AD or amnestic mild cognitive impairment (MCI) versus controls. Lipoprotein Ap distribution was determined in fasted plasma. For assessment of chylomicron homeostasis in the postabsorptive state, subjects were bled 4 h after a low-fat meal. The main outcome measures were plasma lipoprotein Aβ isoform distribution and lipid homeostasis. Results: We found the majority of plasma Ap to be associated with triglyceride-rich lipoproteins (TRLs) encompassing chylomicrons, VLDL and IDL. For all lipoprotein groups, Aβ 1-40 was the predominant isoform, accounting for approximately 50% of the total. Thereafter, equivalent amounts of the isoforms 1 -42, 2-40,1 -38,1 -37 and 1-39 were found. Aβ 1 - 37 , Aβ 1 - 38 and Aβ 2-40 isoforms were significantly enriched within the TRL fraction of AD/MCI subjects and similar trends were observed for isoforms Aβ 1-39 , Aβ 1-40 and Aβ 1-42 . Lipoprotein-Ap was inversely associated with plasma total- and LDL cholesterol. AD/MCI subjects were not dyslipidaemic, however, there was evidence of accumulation of chylomicrons in the postabsorptive state. Conclusions: Our data show that Ap was found to be associated with plasma lipoproteins, especially those enriched with triglyceride. We find that Ap may be increased in normolipidaemic AD subjects, commensurate with possible disturbances in postprandial lipoprotein homeostasis.