Approaches to palliative therapies for Alzheimer's disease.
Alzheimer's disease is a progressive neurodegenerative disease characterized by gradual and increasing loss of cognitive function and behavioral abnormalities. The formation of beta-amyloid plaques and neurofibrillary tangles are recognized as the key pathologies of the disease. Changes in the levels of various key neurotransmitters has been noted in patients with Alzheimer's disease and may represent the earliest biochemical casualty, preceding or signifying the onset of the disease. Over the last 20 years a number of approaches to the palliative treatment of Alzheimer's disease have been scrutinized. The majority of effort has been focused on cognitive dysfunction, as this is the initial and key debilitating symptom of the disease. The identification and commercial development of the acetylcholinesterase inhibitors has, until recently, virtually dominated the field, and although efficacy has been demonstrated, the clinical results suggest alternate approaches are warranted. This review will highlight those palliative approaches that have focused on the improvement of learning and memory and not on the disease-modifying strategies of the beta-amyloid, tau phosphorylation or other neurodegenerative hypotheses.
Robichaud
Albert J
AJ
Chemical & Screening Sciences, Wyeth Research, Princeton, New Jersey 08543-8000, USA. robicha@wyeth.com
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D002491:Central Nervous System Agents / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D010166:Palliative Care; D011956:Receptors, Cell Surface / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
D002491:Central Nervous System Agents; D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D011956:Receptors, Cell Surface; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4