Webber KM, Raina AK, Marlatt MW, Zhu X, Prat MI, Morelli L, Casadesus G, Perry G, Smith MA.
The cell cycle in Alzheimer disease: a unique target for neuropharmacology.
Mech Ageing Dev. 2005 Oct;126(10):1019-25.
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This is a thoughtful review of an underinvestigated but potentially important pathway to neurodegeneration in AD and other related disorders.
This is an intriguing hypothesis, that cell cycle entry coincident with oxidative stress could initiate all known pathological events in Alzheimer disease. It's definitely worth thinking about and testing.
If a disturbed cell cycle was a primary "cause" of AD, as Webber et al. conjecture, how could this explain the phenomenon of twin discordance, or different AD rates in different populations? If Webber et al. cannot take into account such factors—which support a primary nutritional factor—then a disturbed cell cycle is merely a secondary phenomenon, and is probably itself caused by lipid peroxidation by-products, diffusing to the nucleus from a peroxidized neuronal membrane.
The very earliest changes in AD are what I have observed for 10 years in my patients consuming refined vegetable oil—amnesia, glare sensitivity, and night-blindness. I presume that the underlying neuronal lipid peroxidation, arising in vitamin E-deficient synaptic membranes, would give rise to cell cycle problems, as well as to isoprostane formation and ethane exhalation, both of which are measurable, ultra early markers of AD pathology.
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