Antibody Research and Alzheimer's Disease

The incidence of the disease in people over 65 will also evolve with the aging of the population. It is therefore urgent to seek effective treatments for the management or prevention of such diseases.

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What is Alzheimer's disease?

Alzheimer's disease is a progressive neurodegenerative disease. It is characterized by

• Memory loss
• Difficulty working with numbers
• Confusion around time and place
• Difficulty in judging the distance
• Difficulty identifying colors
• Difficulty reading
• Forget the words
• Anxiety and depression

Alzheimer's disease has a poor prognosis, with people living usually between 3 and 11 years after diagnosis. However, some people may live more than 20 years after diagnosis.

Biomarkers for Alzheimer's disease

Alzheimer's disease is badociated with the breakdown of neural pathways in the brain. Cellular dysfunction results from the development of senile plaques composed of β-amyloid peptide (Aβ), which has been identified as the root of the pathogenesis of Alzheimer's disease.

Anti-Aβ antibody treatments are the most advanced treatments currently available. However, some 2018 studies have shown that all Aβ proteins are not as harmful as we thought. Intraneuronal accumulation of neurofibrillary tangles (NFT) is also present in Alzheimer's disease.

One of the current treatments for Alzheimer's disease is the inhibition of acetylcholinesterase, intended to increase the amount of acetylcholine in the brain; this therapy improves communication between the cells. Another therapy, the N-methyl-D-aspartate (NMDA) receptor antagonist, is used to block the effects of large amounts of glutamate in the brain. However, none of these treatments can cure.

Currently, there is no effective treatment to change the course of the disease, since Alzheimer's disease often begins decades before the person manifests symptoms. Therefore, therapies aim to prevent the development of Aβ plaques or to eliminate them.

Research is underway on antibodies for the treatment of Alzheimer's disease

Immunization treatments using antibodies have been developed to treat Alzheimer's disease, but they are not clinically available due to serious side effects. However, pbadive immunization, which uses already formed monoclonal antibodies, has been used to attempt to clean Aβ plaques.

This treatment has shown great promise in mice. However, studies also show that only about 0.1% of the monoclonal antibodies administered reach the brain. The blood-brain barrier, a semi-permeable membrane that blocks access to many proteins, cells and particles, is thought to be the cause.

The use of bispecific antibodies (artificial proteins capable of binding to two different types of antigens at the same time) could help avoid this problem if they are able to bind to a receptor of the blood-brain barrier and the targeted antigen. A number of these types of antibody treatments are available.

One treatment option uses a fully humanized monoclonal antibody that binds to neurotoxic amyloid proteins in the brain and promotes their elimination. However, despite its efficacy in reducing amyloid brain plaques and hyperphosphorylated tau protein in cerebrospinal fluid, it did not substantially improve cognitive abilities during trials. Trials were stopped early when adverse effects of vasogenic edema and microhemorrhages were reported.

A second treatment option is a monoclonal antibody that binds Aβ peptides that create plaques in the brain. It has been used in combination with acetylcholinesterase inhibitors or NMDA in trials, but has not shown improvement in patients with moderate Alzheimer's disease.

What is the tau hypothesis?

Excessive or abnormal phosphorylation of tau proteins converts normal tau protein into paired helical filament tau (PHF-tau) and NFT protein. Tau proteins are a family of six isoforms ranging in size from 352 to 441 amino acids.

The six isoforms are found, often in hyperphosphorylated forms, as pairs of helical filaments in Alzheimer's disease. Hyperphosphorylation is caused by mutations that alter the function and isoform expression of tau.

The process by which tau protein accumulates without the presence of mutations is unknown, but may be related to increased phosphorylation, protease action, or polyanion exposure. Hyperphosphorylated tau creates insoluble PHF structures that damage cytoplasmic function and can lead to cell death.

The tau hypothesis is currently one of the most popular theories regarding the development of Alzheimer's disease. Drugs are being developed to target processes involving tau protein, and trials are underway. However, this theory is not considered complete or definitive.

Antibody Treatments for Familial Alzheimer's Disease

Familial cases of Alzheimer's disease account for about 3% of all cases. The risk of developing Alzheimer's disease in patients with the genetic mutation of familial Alzheimer's disease is 100%. There are now clinical trials of monoclonal antibody therapies that target beta-amyloid plaques in the brain.

In other populations at high risk of developing Alzheimer's disease, studies have been conducted on monoclonal antibodies, active vaccines, and inhibitors of the beta-amyloid precursor protein (APP) 'APP to turn into neurotoxic types of Aβ.

In addition, human studies have been conducted to study the safety and tolerability of an immunotherapy vaccine in patients with Alzheimer's disease, as well as its effects on the antibody response. The final conclusions about whether active or pbadive beta immunotherapy with anti-amyloid drugs can either delay or prevent the onset of Alzheimer's disease have not been drawn.

Further reading