Monoamine oxidase-B inhibitors in the treatment of Alzheimer's disease.

The monoamine oxidase-B (MAO-B) inhibitor L-deprenyl (Selegiline) is effective in treating Parkinson's disease and possibly Alzheimer's disease, with a concomitant extension of life span. It has been suggested that the therapeutic efficacy of L-deprenyl may involve actions other than the inhibition of the enzyme MAO-B. This article reviews some novel actions of L-deprenyl and suggests that stimulation of nitric oxide (NO) production could be central to the action of the drug.

Vascular actions of estrogen and Alzheimer's disease.

Women are two to three times more likely to develop late-onset Alzheimer's disease (AD) than age-matched men. A large number of observational reports and a few randomized clinical trials have indicated that estrogen replacement therapy (ERT) may retard the development and severity of dementia in postmenopausal women. A chronic inflammatory reaction mediated by abnormal deposition of proteins such as amyloid-beta (A beta) is central to the pathology of AD.

L-deprenyl: nitric oxide production and dilation of cerebral blood vessels.

The monoamine oxidase-B inhibitor L-deprenyl (Selegiline) is effective in treating Parkinson's disease and possibly Alzheimer's disease. The neuroprotective property of L-deprenyl may be unrelated to the inhibition of monoamine oxidase-B. Since nitric oxide (NO) modulates activities including cerebral blood flow and memory, we examined the effect of L-deprenyl on NO.

In vivo vascular damage, leukocyte activation and inflammatory response induced by beta-amyloid.

beta-amyloid toxicity is central to the pathology of Alzheimer's disease. Recent evidence implicates vascular dysfunction as a contributing factor to the dementia of Alzheimer type. Using intravital microscopy we demonstrate that in vivo administration of beta-amyloid produces extensive vascular disruption including endothelial and smooth muscle damage, adhesion and migration of leukocytes across arteries and venules.