Therapeutic strategies for Alzheimer's disease based on new molecular mechanisms
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Background and objective: Alzheimer's disease (AD) ? the main cause of dementia ? is characterized by the presence of neuritic plaques containing the amyloid-beta peptide (A beta) and an intraneuronal accumulation of tubule-associated protein called tau. The current and future therapeutic strategies for AD will be discussed. Currently available treatment used in AD is based on acetylcholinesterase inhibitors, since in the course of AD there is a substantial loss in cholinergic neurons. Another registered drug used in more severe AD is NMDA antagonist ? memantine. Available strategies for AD include vitamin supplementation for reducing homocysteine levels, statins and non-steroidal anti-inflammatory drugs. The big hope of the last few years ? vitamin E and estrogen supplementation have not been proved efficient, but more studies are needed. There are several strategies aimed at acting directly on A beta or amyloid precursor protein (APP) processing: vaccination with A beta peptide, A beta passive immunization, beta and gamma secretases inhibitors. Nerve growth factors and neurotrophines could also be targeted by new therapies. Conclusions: a better understanding of the role of APP processing and folate and homocysteine in neuronal homeostasis throughout life consist revealing novel and relatively inexpensive approaches for preventing and treating AD.
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D. Religa, Neurotec, Section of Experimental Geriatrics, Karolinska Institutet, Stockholm, Sweden