Plasma Lipoprotein ß-amyloid in subjects with Alzheimer's disease or mild cognitive impairment

Background: Plasma amyloid beta-peptide (A beta) 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-A beta isoforms.Methods: This involved a case-control study of subjects with AD or amnestic mild cognitive impairment (MCI) versus controls. Lipoprotein A beta 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 A beta isoform distribution and lipid homeostasis.Results: We found the majority of plasma A beta to be associated with triglyceride-rich lipoproteins (TRLs) encompassing chylomicrons, VLDL and IDL. For all lipoprotein groups, A beta(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. A beta(1-37), A beta(1-38) and A beta(2-40) isoforms were significantly enriched within the TRL fraction of AD/MCI subjects and similar trends were observed for isoforms A beta(1-39), A beta(1-40) and A beta(1-42). Lipoprotein-A beta 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 A beta was found to be associated with plasma lipoproteins, especially those enriched with triglyceride. We find that A beta may be increased in normolipidaemic AD subjects, commensurate with possible disturbances in postprandial lipoprotein homeostasis.