Alzheimer’s disease (AD) and dementia are associated with the presence of amyloid-beta (Aβ) peptide and tau protein deposits within neural fibers. These deposits form plaques in the brain’s vascular network and cause tangles in neural fibers, both of which hinder brain function. Aβ plaque reduction therapies have been rather unsuccessful. As a result, scientists and researchers studying AD have changed their perspective and have begun to tackle Aβ prevention therapies that target Aβ through the blood-brain barrier, as opposed to the plaque that already exists in the neurofibrillary tangles. In other words, they are attacking the monster before it fully forms.
How are they doing this?
The technique of plasmapheresis has been tested as a new form of AD prevention therapy. The process of plasmapheresis is similar to giving blood. In fact, you are giving blood, but only a portion of it. Plasma makes up about 55% of the blood in our bodies, with the remainder being red and white blood cells. During plasmapheresis, plasma is removed along with its constituents and the patient’s blood cells are returned to them in a solution of saline [1]. Albumin, one of the most prominent proteins in plasma, binds Aβ. In fact, about 90% of the circulating Aβ is bound to albumin. Aβ clusters in the brain are associated with low levels of soluble Aβ in the cerebrospinal fluid (CSF). It is expected that removing the albumin-bound Aβ in plasma would increase transport of Aβ from the CSF to plasma in attempt to restore homeostasis. This process would then restore the balance between brain and blood Aβ levels, decreasing the burden of Aβ on the brain. As an added bonus, other toxic and harmful substances that reside in plasma are removed by this treatment [2].
The Alzheimer’s disease Management by Albumin Replacement (AMBAR) clinical trial examines the effectiveness of this technique in treating AD and dementia, which is measured by the delay in cognitive decline. Preliminary pilot and phase II studies involving the replacement of Aβ-bound albumin that instigates the diffusion of CSFAβ demonstrated promising results in patients. Cognitive abilities, specifically memory and language functions, as well as blood flow in the brain were improved with plasmapheresis treatment. The positive effects lasted after the treatment period had ended, too. [2].
A new study has since been conducted to collect additional data on the efficacy of this treatment and further evaluate the favorable findings of the preliminary studies, though this time, with the addition of immunoglobulin (IVIG) to the albumin replacement solution to correct a possible immunological defect caused by plasma depletion [2]. The trial consists of 364 patients with mild to moderate AD that have been randomly separated into four groups: 3 groups with varying concentrations of both albumin and IVIG and one placebo group. Treatment intervention lasted 14 months overall. During the initial 6 weeks, the patients were subject to intensive therapeutic plasma exchange. The remaining 12 months were for monthly maintenance low-volume plasma exchanges. At each of these treatment sessions, CSF was collected before and after the exchange. Cognition was assessed with the Mini-Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) [2]. As was observed in the preliminary phase II study, patients treated by plasmapheresis with albumin and IVIG successfully modified the concentration of Aβ in CSF and plasma and treated patients score higher on cognitive assessments than untreated control patients [2]. Thus, the AMBAR trial demonstrated that, though invasive, the combination albumin and IVIG plasmapheresis approach demonstrated clinical efficacy in that it slowed the cognitive decline of patients with mild to moderate AD.
So yes, one could say that plasmapheresis provides a new perspective, and a successful one at that, on treatment and prevention strategies for AD.
Previous approaches to dementia and AD treatment and prevention revolved around either a drug or lifestyle intervention. The issue with drugs as treatment is that they require extensive means of approval from the Food and Drug Administration companies must adhere to strict regulations even after market approval. Lifestyle intervention entails adapting healthy daily habits of a nutritious diet, adequate physical activity, stress management, and sufficient sleep. Dr. Richard S. Isaacson developed an approach known as clinical precision medicine that customizes lifestyle recommendations based on an individual’s risk of dementia. This approach, though, requires a significant amount of further research to identify which interventions and recommendations actually prevent cognitive decline. So far, all that is known that modifying one’s lifestyle in a general sense is beneficial to brain health in that it delays the onset of dementia [3]. Plasmapheresis, on the other hand, is neither a drug-based nor lifestyle-based method of treatment. Instead, it rids the body of the malicious substances that contribute to plaque build-up that is observed in AD and dementia patients.
References
[1] American Red Cross Blood Services. (n.d.). Plasma Information.
[2] Boada, M., et al. (2019). Plasma exchange for Alzheimer’s disease Management by Albumin Replacement (AMBAR) trial: Study design and progress. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 5(1), 61-69. doi:10.1016/j.trci.2019.01.001
[3] Isaacson, R. S.,et al. (2019). Individualized clinical management of patients at risk for Alzheimer’s dementia. Alzheimer’s & Dementia, 15(12), 1588-1602. doi:10.1016/j.jalz.2019.08.198