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TThis study from the AMBAR (Alzheimer Management by Albumin Replacement) phase 2b/3 trial examined the effects of plasma exchange with albumin replacement (PE-Alb) on inflammatory biomarkers in mild-to-moderate Alzheimer’s disease (AD) patients. The goal was to investigate how PE-Alb, which aims to remove neurotoxic amyloid-beta and other pathological substances from the bloodstream, influences inflammation—potentially contributing to AD progression.

Methodology:

• 23 inflammatory biomarkers were measured in serum and cerebrospinal fluid (CSF) of 105 PE-treated and 37 placebo patients.
• Biomarkers were evaluated at multiple time points using a mixed model for repeated measures (MMRM) approach, with adjustments for age, baseline cognitive scores (MMSE), and baseline biomarker levels.

Results:

• 19 biomarkers in serum and 11 in CSF were evaluable.
• Six serum biomarkers showed significant changes in PE-treated patients compared to placebo, with some showing reductions as early as 1.5 months and persisting through the 14-month study.
• In CSF, two biomarkers showed significant reductions by the 2-month mark.

Conclusion: The PE-Alb treatment in AMBAR led to changes in inflammatory profiles in both serum and CSF, supporting a potential multimechanism therapeutic effect. These inflammatory changes may contribute to the slowing of AD progression, aligning with the theory that peripheral inflammation plays a role in AD pathology.