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CNS Drugs

Erschienen in:

01.12.2005 | Leading Article

The Development of Anti-Amyloid Therapy for Alzheimer’s Disease

From Secretase Modulators to Polymerisation Inhibitors

verfasst von: Dr Paul S. Aisen

Erschienen in: CNS Drugs | Ausgabe 12/2005

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Abstract

The leading hypothesis of the pathophysiology of Alzheimer’s disease holds that the pivotal event is cleavage of the amyloid precursor protein to release intact the 42-amino-acid amyloid-β peptide (Aβ); this hypothesis best explains the known genetic causes of Alzheimer’s disease. If this theory is correct, optimal strategies for altering the disease process should be directed toward modifying the generation, clearance and/or toxicity of Aβ. Aβ is highly aggregable, spontaneously assuming a β-sheet conformation and polymerising into oligomers, protofibrils, fibrils and plaques. The relative contribution of the various forms of Aβ to neuronal dysfunction in Alzheimer’s disease remains uncertain; however, recent evidence implicates diffusible oligomeric species.

This article reviews the range of strategies that have been investigated to target Aβ to slow the progression of Alzheimer’s disease, from secretase modulators to anti-polymerisation agents. One amyloid-binding drug, tramiprosate (3-amino-1-propanesulfonic acid; Alzhemed™), which is effective in reducing polymerisation in vitro and plaque deposition in animals, has now reached phase III clinical trials. Thus, it is plausible that an effective anti-amyloid strategy will become available for the treatment of Alzheimer’s disease within the next few years.

1. The use of trade names is for product identifcation purposes only and does not imply endorsement.

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Titel: The Development of Anti-Amyloid Therapy for Alzheimer’s Disease
From Secretase Modulators to Polymerisation Inhibitors
verfasst von: Dr Paul S. Aisen
Publikationsdatum: 01.12.2005
Verlag: Springer International Publishing
Erschienen in: CNS Drugs / Ausgabe 12/2005
Print ISSN: 1172-7047
Elektronische ISSN: 1179-1934
DOI: https://doi.org/10.2165/00023210-200519120-00002

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