Results are due soon from a trial completed by the ADCSs to test the drug selegiline, vitamin E, and their combination for AD. Selegiline, or deprenyl, is an FDA-approved therapy for Parkinson’s disease that increases the supply of dopamine. Another neurotransmitter, dopamine is decreased in AD, although not to the same extent as acetylcholine. Like vitamin E, selegiline is an anti-oxidant.
One long-standing theory of aging suggests that the buildup of damage due to oxidation causes nerve cells to degenerate. Scientists believe that free radicals generated through oxidative mechanisms play a role in AD, cancer, and many other diseases. A free radical is a molecule with an unpaired electron in its outer shell. Normal metabolism produces free radicals of oxygen with unpaired electrons. The body produces free radicals to help cells in certain ways, such as in fighting infections. But, having too many free radicals is bad for cells. Free radicals are extremely reactive; they will latch readily onto other molecules, such as a part of the cell membrane or a piece of deoxyribonucleic acid (DNA). This can set off a chain reaction, releasing chemicals that can harm cells.
In AD, free radicals are suspects for several reasons. They attack molecules of fat in nerve cell membranes and may upset the delicate membrane machinery that regulates what goes into and out of a cell, such as calcium. In addition, oxidation may alter proteins, and these alterations may be associated with the development of AD. Some of these oxidative changes are found in amyloid plaques in AD. Researchers have shown that in neuritic plaques, beta-amyloid causes the release of free radicals. All of the above are changes that cannot be reversed. Reactions like those mentioned also produce several free radical oxidation molecules that may target the internal support structures of nerve cells.
Studies of compounds that fight oxidation–such as the ADCS trial of selegiline and vitamin E–put researchers one step closer to understanding processes that damage cells in AD and finding ways to treat and possibly prevent AD.
Source: Connections Magazine [Volume 6(1), Spring 1997]
Aisen, P.S.; Davis, K.L. Inflammatory Mechanisms in Alzheimer’s Disease: Implications for Therapy. American Journal of Psychiatry. 151(8): 1105-1113. August 1994.
Paganini-Hill, A.; Henderson, V.W. Estrogen Deficiency and Risk of Alzheimer’s Disease in Women. American Journal of Epidemiology. 140(3): 256-261. August 1, 1994.
Rogers, J.; et al. Clinical Trial of Indomethacin in Alzheimer’s Disease. Neurology. 43(8): 1609-1611. August 1993.
Simpkins, J.W.; Singh, M.; Bishop, J. The Potential Role for Estrogen Replacement Therapy in the Treatment of the Cognitive Decline and Neurodegeneration Associated With Alzheimer’s Disease. Neurobiology of Aging. 15(Suppl 2): S195-S197. 1994.
Stewart, W.F.; et al. Risk of Alzheimer’s Disease and Duration of NSAID Use. Neurology. 48(3): 626-632. March 1997.
Tang, M.X.; et al. Effect of Oestrogen During Menopause on Risk and Age at Onset of Alzheimer’s Disease. The Lancet. 348(9025): 429-432. August 17, 1996.
Thal, L. Future Directions for Research in Alzheimer’s Disease. Neurobiology of Aging. 15(Suppl 2): S71-S72. 1994.
Whitehouse, P.J. Cholinergic Therapy in Dementia. ACTA Neurology Scandinavia. Suppl 149: 42-45. 1993.