Immunotherapy against amyloid-β in alzheimer’s disease: An overview

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Abstract

Therapeutic options in Alzheimer’s disease (AD) are limited to symptomatic treatments that show only modest clinical effects. Disease-modifying treatments are urgently needed, and the amyloid cascade hypothesis thus far provides the best basis for the development of such therapies. Preclinical studies in mouse models of AD showed that immunization with amyloid-β (Aβ) as well as passive vaccination with monoclonal antibodies against Aβ may be effective in preventing and treating AD. This has led to the development and testing of immunotherapeutic agents in patients with prodromal AD or AD dementia. Passive immunotherapy with monoclonal antibodies against several Aβ species has been tested in phase 3 clinical trials, with thus far disappointing results. Whether the dosage level, target specificity, and/or stage of the disease is to be blamed for these failures is not fully clear. New mAbs specifically aimed at protofibrils of Aβ species that are thought to be most toxic have been developed and are currently being tested in phase 1 and 2 clinical trials. The first active immunotherapy with AN1792 was halted because of severe side effects. New-generation active vaccination programs with compounds avoiding inflammatory T cell activation are in clinical development. Amyloid-related imaging abnormalities (ARIA) consisting of cerebral edema (ARIA-E) or hemorrhage (ARIA-H) are side effects associated with immunotherapy. It has been suggested that immunotherapy may be most effective when administered early in the disease course, and several studies with mAbs in subjects with preclinical AD are now being performed.
Original languageEnglish
Title of host publicationMethods in Pharmacology and Toxicology
PublisherHumana Press Inc.
VolumePartF1
DOIs
Publication statusPublished - 2016

Publication series

NameMethods in Pharmacology and Toxicology
ISSN (Print)1557-2153
ISSN (Electronic)1940-6053

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