Application of Antibody Fragments Against Aβ With Emphasis on Combined Application With Nanoparticles in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and accumulating evidences suggest a key role of amyloid-β (Aβ) peptide in the pathogenesis of AD. According to the amyloid cascade hypothesis, the imbalance of producing and clearing Aβ is the beginning of neurodegeneration and dementia. Consequently, immunotherapy becomes popular through using antibodies against Aβ. However, many studies of monoclonal antibodies were stopped because adverse effects appeared or there were no evident benefits observed. Some antibody fragments have many advantages over monoclonal antibodies, such as small sizes, lack of the crystallizable fraction (Fc) and so on. There are three main antibody fragments, including single chain variable fragments (scFvs), Fab fragments and single-domain antibody fragments. Nanoparticles can facilitate the entry of drug molecules across the blood-brain barrier, making them become excellent carriers. Various kinds of nanoparticles have been applied in the treatment of AD. The combination of nanoparticles and antibody fragments against amyloid-β can be used in the diagnosis and treatment of Alzheimer’s disease. In this review, we summarize the progress of antibody fragments against amyloid-β in AD, focusing on the combined application with nanoparticles in the diagnosis and treatment of AD.

Oxidative Stress and Beta Amyloid in Alzheimer’s Disease. Which Comes First: The Chicken or the Egg?

“…In the last 30 years, many authors supported the hypothesis of the “amyloid cascade” that considers Aβ to possess a crucial role in the pathogenesis of the disease [ 26 , 27 , 28 , 29 , 30 ]. According to this theory, the accumulation and deposition of Aβ is responsible for Tau aggregation and, therefore, for the cognitive and mnemonic decline observed in AD patients [ 31 ].…”

Current study on diagnosis and treatment of Alzheimer’s disease by targeting amyloid b-protein

“…Nanoparticle (NP) mediated drug delivery systems prove to be a potential means of enhancing brain tissue-targeted drug transport through BBB [55]. Since nanoparticles can be used as drug delivery carriers across the BBB, the combination of nanoparticles and antibody fragments has been used to diagnose AD [49].…”

Amyloid β, Lipid Metabolism, Basal Cholinergic System, and Therapeutics in Alzheimer’s Disease

“…However, it also prevents access to most drugs, resulting in reduced bioavailability and compromising their therapeutic effects. In this way, several alternative and cutting-edge approaches have been proposed for the treatment of AD, such as nanomaterials, antibodies, stem cell transplantation, and nucleic acid insertion [ 246 , 247 , 248 ].…”

“…Therefore, the use of nanomaterials has been proposed to decrease these adverse effects and enhance targeting potential with lower doses [ 253 , 254 ]. These nanomaterials are considered safe, capable of mimicking and modifying biological processes, and demonstrated potential as delivery carriers to treat AD [ 247 , 255 ]. For this purpose, experimental in vitro, ex-vivo, and in vivo procedures have been developed administering the nanomaterials by oral inhalation and intravenous routes to the animal used [ 254 ].…”