An update on drug treatment options of Alzheimer%26apos;s disease

作者：Allgaier Michael; Allgaier Clemens^*

来源：Frontiers in Bioscience, 2014, 19: 1344-1354.

• Alzheimer%26apos
• s disease
• Acetylcholine esterase inhibitor
• Memantine
• NMDA
• Beta-amyloid
• Neurofibrillary tangles
• Tau hyperphosporylation
• Review

Alzheimer%26apos;s disease (AD) is characterized by progressive decrease in cognitive function and loss of short-term memory known to be associated with a dysfunction of the cholinergic system. The pathological hallmarks of AD are beta-amyloid (Abeta) plaques and neurofibrillary tangles (NFTs) consisting of hyperphosphorylated tau. Hypercholesterolemia and disturbances in glucose metabolism are another risk factors. During the last two decades therapeutic strategies were mainly targeting the Abeta hypothesis. As this approach virtually failed to show a significant clinical benefit research on potential therapeutics has been shifted to tau pathology. However, also this approach has as yet not yielded in new therapeutics. Hence, rebalancing the cholinergic input to improve the cognitive symptoms of AD by inhibition of acetylcholine esterase (AChE) is still the only mechanistic target in addition to N-methyl-D-aspartate (NMDA) receptor blockade by memantine that can be addressed by currently approved medications. Despite the fact that the available AChE inhibitors are directed at an identical target they exhibit some pharmacodynamic and pharmacokinetic features that should be considered when used clinically.

• 出版日期2014-6-1