Alzheimer's disease: an overview of current and emerging therapeutic strategies.
Alzheimer's Disease (AD) is a progressive neurodegenerative disease that is prevalent among the elderly. It is a heterogeneous disease involving a number of genetic components, risk factors and other poorly defined elements that all impact on the accumulation of beta-amyloid peptide (Abeta). Current understanding of pathology, biochemistry and genetics strengthens the notion that Abeta is potentially the common pathogenic agent in an apparent convergence of various mechanisms leading to the decline of cognitive function and neuronal loss. While many issues remain controversial, recent evidence attributing Abeta accumulation to cognitive decline in humans, coupled to the demonstrated improvement of cognitive function following Abeta immunization in pre-clinical models, strongly supports the "amyloid hypothesis" and a central role for Abeta; in the pathophysiology and etiology of AD. These and other observations endorse the notion that therapeutic strategies targeting the inhibition of Abeta accumulation by the use of protease inhibitors,immunization or other strategies, may provide disease-altering interventions to the development and progression of AD. The only approved and marketed treatments currently available for AD are the acetylcholinesterase inhibitors, a palliative strategy aimed at the temporary improvement of cognitive function. The purpose of this overview is to provide a brief understanding of key events leading to the progression of AD and to highlight a few of the current and most promising therapeutic strategies that one day might be available for the treatment of AD.
Jacobsen
J Steven
JS
Neuroscience Discovery Research, Wyeth Research, CN-8000, Princeton, New Jersey, 08543-8000, USA. jacobss@wyeth.com
D000544:Alzheimer Disease / Q000378:metabolism / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D015195:Drug Design; D005544:Forecasting; D015316:Genetic Therapy; D006801:Humans; D007167:Immunotherapy
D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors