Alzheimer’s disease remains one of the most formidable neurological challenges worldwide. In Australia, more than 400,000 people live with dementia, of which Alzheimer’s is the most prevalent cause. This progressive neurodegenerative disorder results in the gradual loss of memory, reasoning and functional independence, profoundly impacting patients, caregivers, and the healthcare system.
Despite decades of research, curative options are not yet available, and most current treatments focus on symptomatic relief rather than disease modification. However, novel therapies are emerging that aim to alter the underlying pathological processes. Among these, therapeutic plasma exchange (TPE) is attracting growing interest as a potential adjunctive intervention.
Understanding therapeutic plasma exchange and Alzheimer’s disease
TPE, also known as apheresis, is an extracorporeal procedure in which plasma is separated from whole blood, removed, and replaced with albumin or other plasma substitutes.
TPE is thought to influence Alzheimer’s disease through two complementary mechanisms:
- The “peripheral sink” hypothesis suggests that lowering plasma levels of soluble or albumin-bound amyloid-β (Aβ) shifts the equilibrium between the central nervous system and the periphery, encouraging efflux of Aβ from the brain.
- TPE may modulate systemic inflammation by removing circulating cytokines and chemokines. Given that neuroinflammation is increasingly recognised as a driver of disease progression, this immunomodulatory effect may contribute to the observed clinical benefits.
These mechanisms are biologically plausible and supported by preliminary biomarker data.
The evidence base: AMBAR and beyond
The AMBAR trial (Alzheimer Management by Albumin Replacement) is the largest and most comprehensive investigation of TPE in Alzheimer’s to date. Conducted across multiple international centres, this randomised, placebo-controlled study assessed the effects of periodic plasma exchange with albumin replacement in patients with mild to moderate Alzheimer’s disease.
Key findings included:
- Cognitive outcomes: Patients undergoing TPE experienced a slower rate of decline in memory, language, and executive function compared to controls
- Neuropsychiatric improvements: Treated patients demonstrated fewer symptoms of anxiety, apathy, and agitation.
- Functional benefits: Caregiver-reported measures suggested improved daily functioning and enhanced quality of life.
Complementary analyses revealed changes in inflammatory markers within both blood and cerebrospinal fluid, indicating that TPE exerts systemic and central anti-inflammatory effects. These findings are consistent with the hypothesis that Alzheimer’s progression is influenced not only by protein aggregation but also by chronic dysregulation of immune and inflammatory pathways.
Future directions in dementia care
TPE represents a paradigm shift from symptomatic management toward disease-modifying therapy. While not curative, it offers the possibility of altering disease trajectory in selected patients, aligning with broader efforts to intervene earlier and more effectively in neurodegenerative conditions.
While the AMBAR results are encouraging, they also highlight the complexity of translating biological effects into long-term clinical benefit. Several questions remain unanswered. Long-term efficacy data are limited, and further trials are required to validate findings, establish best practice protocols, and assess cost-effectiveness in routine care. Biomarker-driven patient stratification may eventually identify subgroups most likely to benefit, improving clinical precision.
At present, TPE should be considered an emerging therapeutic option, best pursued in specialist centres equipped for advanced interventions and supported by multidisciplinary expertise.
Monash House Private Hospital’s role
Monash House Private Hospital provides a supportive, specialist-led environment where advanced therapies such as therapeutic plasma exchange (TPE) can be explored. Our well-equipped facilities and highly skilled nursing and medical teams support VMOs in delivering complex treatments with a focus on safety and patient care.
As part of our commitment to clinical innovation, Monash House works closely with international leaders in apheresis, including Dr Dobri Kiprov of Global Apheresis, San Francisco. Dr Kiprov is widely recognised as a pioneer in the field of therapeutic apheresis and continues to contribute to the advancement of TPE as a potential disease-modifying approach for neurodegenerative disorders. His involvement provides valuable clinical insight and reinforces Monash House’s dedication to evidence-based practice and collaboration at a global level.
Interested in exploring TPE at Monash House?
We encourage referring clinicians to contact our TPE coordination team to review individual cases and determine eligibility for this emerging treatment for Alzheimer’s disease. If you are an HCP and would like to refer directly to our TPE team, please fill in the following referral form.
References
- Alzheimer’s Research Australia, Making Alzheimer’s a distant memory for future generations, https://alzheimersresearch.org.au/, [Accessed 25 September 2025]
- Jeffrey L. Winters; Plasma exchange: concepts, mechanisms, and an overview of the American Society for Apheresis guidelines. Hematology Am Soc Hematol Educ Program 2012; 2012 (1): 7–12. doi: https://doi.org/10.1182/asheducation.V2012.1.7.3797920, [Accessed 25 September 2025]
- Chen, Y., Yu, Y. Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation. J Neuroinflammation 20, 165 (2023). https://doi.org/10.1186/s12974-023-02853-3, [Accessed 25 September 2025]
- Taragano, F., Seinhart, D., Epstein, P., Sylvestre, V., Barañano, C., Otero Castro, V., Sánchez, V., Kilstein, A., González, R., Franco‑Trecu, V., & Costa‑Urrutia, P. (2025). A real‑world study on the safety and efficacy of therapeutic plasma exchange in patients with Alzheimer’s disease. Journal of Alzheimer’s Disease. Advance online publication. https://doi.org/10.1177/13872877251375430, [Accessed 25 September 2025]
- Gonzalo R, Minguet C, Ortiz AM, Bravo MI, López OL, Boada M, Ruiz A, Costa M. Plasma exchange with albumin replacement for Alzheimer’s disease treatment induced changes in serum and cerebrospinal fluid inflammatory mediator levels. Ann Clin Transl Neurol. 2024 Dec;11(12):3280-3291. doi: 10.1002/acn3.52235. Epub 2024 Oct 30. PMID: 39476248; PMCID: PMC11651178, https://pmc.ncbi.nlm.nih.gov/articles/PMC11651178/, [Accessed 25 September 2025]
