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Progress in the development of new drugs in Alzheimer’s disease

  • Published:
The journal of nutrition, health & aging

Abstract

Alzheimer’s disease (AD) is an age-related neurodegenerative disease with a global prevalence estimated at 26.55 million in 2006. During the past decades, several agents have been approved that enhance cognition of AD patients. However, the effectiveness of these treatments are limited or controversial and they do not modify disease progression. Recent advances in understanding AD pathogenesis have led to the development of numerous compounds that might modify the disease process. AD is mainly characterized neuropathologically by the presence of two kinds of protein aggregates: extracellular plaques of Abeta-peptide and intracellular neurofibrillary tangles. Abeta and tau could interfere in an original way contributing to a cascade of events leading to neuronal death and transmitter deficits. Investigation for novel therapeutic approaches targeting the presumed underlying pathogenic mechanisms is major focus of research. Antiamyloid agents targeting production, accumulation, clearance, or toxicity associated with Abeta peptide, are some approaches under investigation to limit extracellular plaques of Abeta-peptide accumulation. We can state as an example: Abeta passive and active immunization, secretases modulation, Abeta degradation enhancement, or antiaggregation and antifibrillization agents. Tau-related therapies are also under clinical investigation but few compounds are available. Another alternative approach under development is neuroprotective agents such as antioxidants, anti-inflammatory drugs, compounds acting against glutamate mediated neurotoxicity. Neurorestorative approaches through neurotrophin or cell therapy also represent a minor avenue in AD research. Finally, statins, receptor for advanced glycation end products inhibitors, thiazolidinediones, insulin, and hormonal therapies are some other ways of research for a therapeutic approach of Alzheimer’s disease. Taking into account AD complexity, it becomes clear that polypharmacology with drugs targeting different sites could be the future treatment approach and a majority of the recent drugs under evaluation seems to act on multiple targets. This article exposes general classes of disease-modifying therapies under investigation.

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Authors and Affiliations

  1. Gérontopôle, Hôpitaux de Toulouse, Toulouse, France

    Antoine Piau, F. Nourhashémi, C. Hein, C. Caillaud & B. Vellas

  2. Inserm U558, F-31073, Toulouse, France

    F. Nourhashémi & B. Vellas

  3. Gérontopôle, Alzheimer’s Disease Research and Clinical Center; Department of Internal Medicine and Clinical Gerontology, University Hospital, Purpan-Casselardit, 170 chemin de Casselardit, 31059, Toulouse, France

    Antoine Piau

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  1. Antoine Piau
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  2. F. Nourhashémi
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  3. C. Hein
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  4. C. Caillaud
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  5. B. Vellas
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Correspondence to Antoine Piau.

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Piau, A., Nourhashémi, F., Hein, C. et al. Progress in the development of new drugs in Alzheimer’s disease. J Nutr Health Aging 15, 45–57 (2011). https://doi.org/10.1007/s12603-011-0012-x

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  • DOI: https://doi.org/10.1007/s12603-011-0012-x

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