What is the rationale for new treatment strategies in Alzheimer's disease?

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is characterized by the abnormal extracellular accumulation of amyloid β-peptide (Aβ) into neuritic plaques and the intraneuronal aggregation of the microtubule-associated protein tau to form neurofibrillary tangles. These molecular events are implicated in the selective damage to neural systems critical for the brain functions that are impaired in AD. Impairment of cholinergic neurotransmission may be an important factor underlying the defects in cognition and memory that characterize AD. Cholinesterase (ChE) inhibitors, such as donepezil, rivastigmine, and galantamine, cause symptomatic improvement by inhibiting the breakdown of the neurotransmitter acetylcholine to increase its synaptic availability and, in the case of galantamine, by also allosterically potentiating nicotinic cholinergic receptors. Other agents, including vitamin E, monoamine oxidase inhibitors, and statins, have shown some benefit in epidemiological studies and clinical trials although compelling evidence of their efficacy is lacking. Memantine, shown to cause cognitive and functional improvement, is not an ChE inhibitor and does not interact with marketed ChE inhibitors. While the mechanism of action of memantine in AD is not known, the principal pharmacologic actions at therapeutic dose are inhibition of ionotropic neurotransmitter receptors, specifically N-methyl-D-aspartate (NMDA), 5-HT3, and nicotinic receptors. Like other NMDA antagonists, memantine causes behavioral activation associated with enhanced cerebral glucose utilization. Studies have shown that memantine can reverse the decreased metabolic activity associated with AD, possibly accounting for its beneficial effects on cognition and global functioning. Memantine also has neuroprotective properties and can inhibit Aβ-induced neurodegeneration.

Original languageEnglish (US)
Pages (from-to)6-12+31
JournalCNS Spectrums
Volume9
Issue number7 SUPPL. 5
StatePublished - Jul 2004
Externally publishedYes

Fingerprint

Memantine
Alzheimer Disease
Cholinesterase Inhibitors
Galantamine
Rivastigmine
Nicotinic Receptors
N-Methylaspartate
Cognition
Pharmacologic Actions
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Receptors, Serotonin, 5-HT3
Neurofibrillary Tangles
Neurotransmitter Receptor
Monoamine Oxidase Inhibitors
Microtubule-Associated Proteins
Amyloid Plaques
Cholinergic Receptors
Vitamin E
Amyloid
Synaptic Transmission

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology

Cite this

What is the rationale for new treatment strategies in Alzheimer's disease? / Rogawski, Michael A.

In: CNS Spectrums, Vol. 9, No. 7 SUPPL. 5, 07.2004, p. 6-12+31.

Research output: Contribution to journalArticle

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