Longitudinal lipidomic analyses in patients undergoing therapeutic plasma exchange with albumin replacement as a treatment for Alzheimer's disease. (20th December 2022)

• Record Type: Journal Article
• Authors: Minguet, Carla; Ortiz, Ana Maria; Gonzalo, Ricardo; Horrillo, Raquel; Núñez, Laura; Ruiz, Agustin; Lopez, Oscar L.; Boada, Mercè; Páez, Antonio; Costa, Montserrat
• Is Part Of: Alzheimer's & dementia. Volume 18(2022)Supplement 6
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-20
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.069273
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Differences in ceramides, glycerides, phospholipids, cholesterol esters and fatty acids (FA) lipid subclasses have been reported between Alzheimer's disease (AD) patients and healthy subjects (Liu et al. Transl Psychiatry 2021;11:344). The AMBAR phase 2b/3 trial is a therapeutic approach for mild‐moderate AD patients (MMSE:18‐26) based on a 14‐month program comprising 18 plasma exchange procedures with albumin replacement (PE‐Alb) to remove neurotoxic Aβ and other pathological substances from plasma, thus slowing AD progression (Boada et al. Alzheimers Dement 2020;16:1412). The aim of this study was to assess PE‐Alb effects on lipidomics across the AMBAR study. Method: 250 metabolomic biomarkers were quantified from serum samples of 309 individuals included in the AMBAR study using high‐throughput proton NMR (Nightingale Health Ltd, Helsinki, Finland). Up to 236 PE‐treated and 73 placebo [sham‐PE] patients’ samples, at 3 time points, were assessed. Raw metabolic levels were log2 normalized and scaled. Biomarkers were analyzed with a mixed model for repeated measures including fixed effects factors for month, treatment group and month * treatment group interaction, adjusted for baseline MMSE, age, sex, BMI, apoε4, lipid‐lowering medication, baseline biomarker levels and patient as a repeated factor. Differences from placebo as fold change (FC) were assessed through month * treatment group interaction term estimates. Result: 57 metabolomic biomarkers showed statistical significance (Adj.p‐value <0.05) of PE‐treated patients compared to placebo at the end of study (EOS, 14 months). All significant metabolites were up‐regulated in PE‐treated patients vs placebo. 45/57 significant metabolites belonged to lipidomic subclasses such as cholesterols (including cholesteryl esters), glycerophospholipids and fatty acids. Polyunsaturated FA (docosahexaenoic acid and linoleic acid), which may have a positive role against AD (Heath et al. Int J Mol Sci 2021;22:11826), were significantly increased at EOS (Adj.p‐value 0.038 and 0.020; linear‐FC=1.2 both), while saturated and monounsaturated FA were not (Adj.p‐value 0.19 and 0.735, respectively). Similarly, phosphatidylcholine levels, reported as altered in AD (Whiley et al. Neurobiol Aging 2014;35:271), were significantly upregulated (Adj.p‐value 0.049, linear‐FC=1.2) at EOS. Conclusion: PE‐Alb procedures used in AMBAR induced changes in lipidomic profiles. This supports the multimechanism basis of AMBAR therapeutic approach that may contribute to slowing AD progression.