Abstract :
Alzheimerʹs 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 Abetapeptide
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
