Role of Human Serum Albumin in the Prevention and Treatment of Alzheimer’s Disease

Abstract—

Alzheimer’s disease (AD) was and remains the main cause of the development of dementia in older patients. This neurodegenerative disease is characterized by a progressive course and belongs to a group of socially significant diseases. There are several hypotheses for the development of AD: the tau hypothesis, the amyloid hypothesis, the cholinergic hypothesis, the hypotheses of oxidative stress and inflammation. The absence of a generally accepted understanding of the etiology and pathogenesis of AD prevents the development of new efficient methods for its treatment and prevention. In clinical practice, cholinesterase inhibitors that alleviate the symptoms of the disease but do not affect its course are widely used. In 2021, a drug for pathogenetic therapy of AD (aducanumab), which contributes to a decrease in the content of amyloid-β peptide (Aβ) in the brain of patients, was for the first time approved. The effect on human serum albumin (HSA), which carries 90% of Aβ in the blood serum and 40–90% of Aβ in the cerebrospinal fluid, is another promising approach to the treatment of AD aimed at removing Aβ from the patient’s central nervous system. In clinical practice, plasmapheresis with a replacement of one’s own HSA with a purified therapeutic albumin preparation has already been tested and demonstrated its efficiency. The enhancement of the interaction of HSA with Aβ through the effect of exogenous and endogenous HSA ligands (such as serotonin, ibuprofen, and some unsaturated fatty acids) is another variant of this approach. The studies in vivo confirm the association of this group of ligands with the pathogenesis of AD. The listed substances belong to well-studied natural metabolites or drugs, which significantly simplifies the development of new methods of therapy and prevention of AD using them. In general, a new direction of scientific studies devoted to the study of HSA as a carrier and depot of Aβ in the blood and cerebrospinal fluid will allow us to expand our understanding of Aβ metabolism and its role in the pathogenesis of AD.