[Aβ immunotherapy for Alzheimer's disease].

Abstract

Alzheimer's disease (AD) is one of the neurodegenerative diseases characterized by the deposition of amyloid-β-protein (Aβ) as senile plaques in the brain parenchyma and phosphorylated-tau accumulation as neurofibrillary tangles in the neurons. Although details of the disease pathomechanisms remain unclear, Aβ likely acts as a key protein for AD initiation and progression, followed by abnormal tau phosphorylation and neuronal death (amyloid-cascade hypothesis). According to this hypothesis, Aβ immunization therapies are created to eliminate Aβ from the brain, and to prevent the neurons from damage by these pathogenic proteins. There are two methods for Aβ immunotherapies: active and passive immunization. Previous studies have shown Aβ removal and improved cognitive function in animal models of AD. Clinical trials on various drugs, including AN1792, bapineuzumab, and solanezumab, have been carried out; however, all trials have failed to demonstrate apparent clinical benefits. On the contrary, side effects emerged, such as meningoencephalitis, vasogenic edema, which are currently called amyloid related imaging abnormalities (ARIA)-E and microhemorrhage (ARIA-H). In neuropathological studies of immunized cases, Aβ was removed from the brain parenchyma and phosphorylated-tau was reduced in the neuronal processes. Moreover, deterioration of the cerebral amyloid angiopathy (CAA) and an increase of microhemorrhages and microinfarcts were described. Aβ is cleared from the brain mainly via the lymphatic drainage pathway. ARIA could stem from severe CAA due to dysfunction of the drainage pathway after immunotherapy. Aβ immunization has a potential of cure for AD patients, although the above-described problems must be overcome before applying this therapy in clinical treatment.

• Authors: Kenji Sakai, Masahito Yamada
• Journal: Brain and nerve = Shinkei kenkyu no shinpo (Brain Nerve) Vol. 65 Issue 4 Pg. 461-8 (Apr 2013) ISSN: 1881-6096 [Print] Japan
• PMID: 23568994 (Publication Type: English Abstract, Journal Article, Review)

Chemical References

• Amyloid beta-Peptides

Topics

• Alzheimer Disease (diagnosis, immunology, pathology, therapy)
• Amyloid beta-Peptides (immunology, metabolism)
• Animals
• Disease Models, Animal
• Humans
• Immunotherapy (adverse effects, methods)