Plasma exchange cuts amyloid plaques in aged Alzheimer’s model mice

Plasma exchange with albumin replacement has reduced amyloid deposition and altered the neuroinflammatory environment in the brains of aged mice engineered to model Alzheimer’s disease, even when the treatment was started only after the animals had reached an advanced stage of pathology. The findings, published in Alzheimer’s Research & Therapy, come from a peer-reviewed study in the APP/PS1 mouse model and add to a small but growing body of work exploring plasma exchange as an alternative approach to amyloid-directed Alzheimer’s therapies.

The research team, led by Suelyn Koerich and Santiago Ramirez with senior author Claudio Soto, treated APP/PS1 mice with monthly plasma exchange beginning at 11 months of age. At this age, the animals had already reached an advanced stage of amyloid pathology in this model, a deliberate design choice that tested whether the intervention could still engage established disease processes rather than preventing them from forming in the first place.

After the treatment period, the researchers quantified biomarkers in brain and plasma samples and used immunofluorescence staining to visualize plaques and microglia, the brain’s resident immune cells. The results showed that the treated animals had significantly reduced levels of insoluble Aβ42 and Aβ40, the two amyloid-beta species most closely associated with plaque formation, along with a reduced overall plaque burden.

The treatment also reshaped the microglial response. Mice that received plasma exchange showed a lower overall microglia burden but a higher degree of microglial engagement per plaque, suggesting that the remaining immune cells were more actively associated with individual amyloid deposits. The authors report that these brain changes were accompanied by higher plasma Aβ levels, a pattern consistent with a shift of amyloid out of brain tissue and into the bloodstream.

Plasma exchange also altered levels of cytokines, signaling molecules of the immune system, that have been linked to Alzheimer’s pathology. However, not every marker of brain injury moved in a direction that would suggest benefit. The neurodegenerative marker NSE and the neuroinflammatory marker GFAP were elevated in both transgenic groups relative to wild-type controls, and they did not differ significantly between the plasma-exchange-treated mice and the sham-treated mice.

That last point matters for interpretation. The study’s authors state explicitly that whether the observed changes in amyloid and inflammation improved the neurodegenerative state of the animals remains unknown. The abstract does not report cognitive testing results, and the paper’s conclusion frames the work as evidence that plasma exchange engages amyloid pathology and the neuroinflammatory milieu at advanced disease stages, not as a demonstration of therapeutic benefit against neurodegeneration itself.

The context for this line of research is the limited success of current Alzheimer’s treatments. According to the study’s background, existing therapies offer limited benefits and many amyloid-targeting approaches have failed, which has pushed researchers toward alternative strategies, including plasma exchange with albumin replacement. While this approach has shown promise as a potential therapy, its effects on Aβ pathology, neuroinflammation and cognitive function had not been fully understood.

Plasma exchange is a procedure in which a patient’s plasma is removed and replaced, in this case with albumin replacement. The rationale explored in this study is that such exchange may influence amyloid dynamics and immune signaling, though the precise mechanisms remain an open question that this mouse work does not fully resolve. Because the intervention was tested in a transgenic mouse model, the findings are preliminary with respect to human disease and cannot be assumed to translate directly to patients.

The authors position these results alongside their previous report as supporting the need for further studies of plasma exchange treatment for Alzheimer’s disease. They specifically call for work on combination therapies and for longitudinal studies covering both preclinical and clinical stages of the disease. Such studies would be needed to establish whether the biochemical and cellular changes observed here correspond to any slowing of neurodegeneration or preservation of cognitive function.

For now, the study’s contribution is a demonstration of feasibility at a late disease stage in an animal model: monthly plasma exchange, begun well after amyloid pathology was established, was associated with reduced insoluble amyloid, altered plaque-associated microglial behavior, higher circulating Aβ and modified cytokine levels, while markers of neurodegeneration and astrogliosis remained unchanged between treated and untreated transgenic animals. The article was published as an open-access research paper on 24 October 2026 and, as an early-shared version, remains subject to further editorial edits before the final version of record.

Subject of Research: Effects of plasma exchange with albumin replacement on amyloid pathology and neuroinflammation in aged APP/PS1 Alzheimer's model mice

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

Article References: Koerich, S., Ramirez, S., Harrison, D., Colpo, G. D., Allison, T., & Soto, C. (2026). Plasma exchange reduces amyloid deposition, modulates neuroinflammation, and microglial response in an advanced stage of pathology in the APP/PS1 mouse model. Alzheimer's Research & Therapy. https://doi.org/10.1186/s13195-026-02241-y

Image Credits: AI Generated

DOI: 10.1186/s13195-026-02241-y

Keywords: plasma exchange, albumin replacement, Alzheimer's disease, amyloid-beta, APP/PS1 mice, microglia, neuroinflammation, Aβ42, Aβ40, cytokines, plaque burden, preclinical study