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Acta Neuropathologica
Erschienen in: Acta Neuropathologica 4/2016

01.04.2016 | Review

Immunotherapies in Alzheimer’s disease: Too much, too little, too late or off-target?

verfasst von: Isabelle St-Amour, Francesca Cicchetti, Frédéric Calon

Erschienen in: Acta Neuropathologica | Ausgabe 4/2016

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Abstract

Years of research have highlighted the importance of the immune system in Alzheimer’s disease (AD), a system that, if manipulated during strategic time windows, could potentially be tackled to treat this disorder. However, to minimize adverse effects, it is essential to first grasp which exact aspect of it may be targeted. Several clues have been collected over the years regarding specific immune players strongly modulated during different stages of AD progression. However, the inherent complexity of the immune system as well as conflicting data make it quite challenging to pinpoint a specific immune target in AD. In this review, we discuss immune-related abnormalities observed in the periphery as well as in the brain of AD patients, in relation to known risk factors of AD such as genetics, type-2 diabetes or obesity, aging, physical inactivity and hypertension. Although not investigated yet in clinical trials, C5 complement system component, CD40/CD40L interactions and the CXCR2 pathway are altered in AD patients and may represent potential therapeutic targets. Immunotherapies tested in a clinical context, those aiming to attenuate the innate immune response and those used to facilitate the removal of pathological proteins, are further discussed to try and understand the causes of the limited success reached. The prevailing eagerness to move basic research data to clinic should not overshadow the fact that a careful preclinical characterization of a drug is still required to ultimately improve the chance of clinical success. Finally, specific elements to consider prior to initiate large-scale trials are highlighted and include the replication of preclinical data, the use of small-scale human studies, the sub-typing of AD patients and the determination of pharmacokinetic and pharmacodynamics parameters such as brain bioavailability and target engagement.
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Metadaten
Titel
Immunotherapies in Alzheimer’s disease: Too much, too little, too late or off-target?
verfasst von
Isabelle St-Amour
Francesca Cicchetti
Frédéric Calon
Publikationsdatum
01.04.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Acta Neuropathologica / Ausgabe 4/2016
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-015-1518-9

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