Boada M, López OL, Olazarán J, Núñez L, Pfeffer M, Paricio M, Lorites J, Piñol-Ripoll G, Gámez JE, Anaya F, Kiprov D, Lima J, Grifols C, Torres M, Costa M, Bozzo J, Szczepiorkowski ZM, Hendrix S, Páez A. A randomized, controlled clinical trial of plasma exchange with albumin replacement for Alzheimer's disease: Primary results of the AMBAR Study. Alzheimers Dement. 2020 Oct;16(10):1412-1425. Epub 2020 Jul 27 PubMed.
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UCC Medical School
The AMBAR clinical study is promising but also raises questions. If plasmapheresis (Apheresis) with plasma exchange to young plasma or to patients’ own filtered plasma with albumin exchange can reduce development of the disease, it may well establish a persuasive reason that Alzheimer’s dementia is mainly a blood-borne disease.
During AMBAR the low and high albumin, with or without IVIG, all have a similar positive effect, with low statistical difference between experimental groups, suggesting the amount of added albumins was not very important. This may be because these proteins significantly exceeded the necessary amount of exchange to sequester the amyloid, or because these proteins are not important at all, and the filtering procedure is more important. Interestingly, therapeutic plasma exchange, which constitutes an extracorporeal blood purification technique designed to remove large-molecular-weight particles from plasma, is a standard procedure for many neurological disorders (Lehmann et al., 2006). Why it was not probed for Alzheimer’s can be explained only by the long history of exclusively brain-borne theory of this disease.
Interestingly, blood transfusion (blood banks do not check for Aβ) itself produces a 1.37-fold higher risk of Alzheimer’s disease. Patients who received a transfusion of washed red blood cells showed a 2.37-fold higher risk of dementia (95 percent CI = 1.63-3.44) than those who did not (Lin et al., 2019).
References:
Lehmann HC, Hartung HP, Hetzel GR, Stüve O, Kieseier BC. Plasma exchange in neuroimmunological disorders: Part 1: Rationale and treatment of inflammatory central nervous system disorders. Arch Neurol. 2006 Jul;63(7):930-5. PubMed.
Lin SY, Hsu WH, Lin CC, Lin CL, Yeh HC, Kao CH. Association of Transfusion With Risks of Dementia or Alzheimer's Disease: A Population-Based Cohort Study. Front Psychiatry. 2019;10:571. Epub 2019 Aug 16 PubMed.
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