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This study from the AMBAR trial investigated the effects of plasma exchange with albumin replacement (PE-Alb) on lipidomic profiles in patients with mild-to-moderate Alzheimer’s disease (AD). Since lipid differences are known between AD patients and healthy individuals, this study aimed to see if PE-Alb could impact lipid biomarkers associated with AD.

Methodology:

• Serum samples from 309 individuals (236 PE-treated and 73 placebo) were analyzed at three time points over the 14-month study.
• A total of 250 metabolomic biomarkers were measured and analyzed using statistical models to compare PE-treated patients with the placebo group, adjusted for factors such as age, sex, baseline cognitive scores (MMSE), and other health variables.

Key Findings:

• By the end of the study (14 months), 57 metabolomic biomarkers showed statistically significant changes in PE-treated patients compared to placebo, with all significant metabolites upregulated in the treatment group.
• Notably, 45 of these 57 metabolites were lipids, including cholesteryl esters, glycerophospholipids, and fatty acids.
• Polyunsaturated fatty acids like docosahexaenoic acid (DHA) and linoleic acid, which may have neuroprotective effects, were significantly increased in PE-treated patients.
• Phosphatidylcholine, a lipid reported to be altered in AD, was also significantly upregulated in the treatment group.

Conclusion: PE-Alb in the AMBAR study led to beneficial changes in lipidomic profiles, especially in lipids linked to AD pathology. These findings support the potential multimechanism therapeutic approach of PE-Alb in slowing AD progression.