Plasma exchange reduces amyloid deposition, modulates neuroinflammation, and microglial response in an advanced stage of pathology in the APP/PS1 mouse model

Current treatments for Alzheimer’s disease (AD) offer limited benefits, and many amyloid-targeting therapies have failed. This has led to exploring alternative approaches, including plasma exchange (PE) with albumin replacement. While this treatment shows promise as a potential therapy, its effect on Aβ pathology, neuroinflammation, and cognitive function is not yet fully understood. APP/PS1 mice received a monthly PE treatment starting at 11 months of age, when the animals had reached an advanced stage of amyloid pathology in this model. Brain and plasma biomarkers were quantified, and immunofluorescence staining of plaques and microglia was performed. Aged APP/PS1 mice subjected to PE showed significantly reduced insoluble Aβ42 and Aβ40 levels, plaque burden, and overall microglia burden while increasing microglia engagement per plaque. These changes were accompanied by higher plasma Aβ levels. PE altered levels of cytokines linked to AD pathology; however, the neurodegenerative and neuroinflammatory markers NSE and GFAP were elevated in both transgenic groups relative to WT controls, but did not differ significantly between PE-treated and sham-treated mice. These findings demonstrate that PE with albumin replacement engages amyloid pathology and the neuroinflammatory milieu in the brain, even at advanced stages of the disease. Whether these changes improved the neurodegenerative state remains unknown. These results, along with our previous report, support the need for further studies on PE treatment for AD, including combination therapies and longitudinal studies at preclinical and clinical stages of the disease.