Abnormal Phospholipid Metabolism in Neurodegenerative Diseases: Elevations in Glycerophosphocholine and Glycerophospho-Ethanolamine Levels in Brain of Alzheimer’s Disease But Not in Down Syndrome Patients
Among the numerous neurotransmitter abnormalities described in brains of patients with Alzheimer’s disease (AD), the decrease in the activity of choline acetyltransferase [the acetylcholine (ACh)-synthesizing enzyme] was first identified (Bowen et al., 1976) and remains the most robust. The cholinergic deficit in is strongly correlated with the cell loss (McGeer et al., 1984) and senile plaques (Perry et al., 1987) characteristic of AD, and probably contributes to Thc amncsia that is so prominent in this disorder. Brains of patients with Down syndrome (DS) have pathological features of AD by the fourth decade of life (Coyle et al., 1988, for a recent review) and develop cholinergic deficits similar to those in AD (Yates, 1983); Any theory that attempts to explain the vulnerability of cholinergic neurons in AD or DS should take into account their unique dual requirement for choline: all cells need choline for incorporation into phosphatidylcholine (PC), a structural component of biological membranes, but cholinergic neurons also need choline for ACh synthesis (Blusztajn and Wurtman, 1983). In disorders like AD, in which the loss of cholinergic neurons presumably causes localized deficiencies in cholinergic tone, surviving neurons may undergo a net degradation of their membrane phospholipids in order to supply sufficient choline to support augmented ACh synthesis and release (Maire and Wurtman, 1985; Ulus et al., 1989). In support of this hypothesis, we now report that concentrations of major metabolites of PC [glycerophosphocholine (GPC)] and of phosphatidylethanolamine (PE) [glycerophosphoethanolamine (GPE)] are significantly increased in AD brains.
KeywordsDown Syndrome Cholinergic Neuron Senile Plaque Down Syndrome Patient Cholinergic Deficit
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- Cunico, R., Anton, G., Mayer, C., Wehr, T., and Sheehan, T.L., 1986, High sensitivity amino acid analysis using a novel automated precolunm derivatization system, BioChromatography, 1: 6.Google Scholar
- Hicks, N., Brammer, M.J., Hymas, N.,and Levy, R., 1987, Platelet membrane properties in Alzheimer and multi-infarct dementias, Alzheimer Disease and Associated Disorders, 1: 90.Google Scholar
- Maire, J-C., and Wurtman, R.J., 1985, Effect of electrical stimulation and choline availability on the release and contents of acetylcholine and choline in superfused slices from rat stiatum, J. Physiol. ( Paris ), 80: 189.Google Scholar
- Perry, E.K., Tomlinson, B.E., Blessed, G., Bergman, K., Gibson, P.H., and Perry, R.H., 1987, Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia, Brit. Med. J., 11: 1457.Google Scholar
- Pettegrew, J.W., Kopp, S•J., Minshew, N.J., Glonek, T., Feliksik, J.M., Tow, J.P., and Cohen, M.M., 1987, 31P nuclear magnetic resonance studies of phosphoglyceride metabolism in developing and degenerating brain: preliminary observations. J. Neuropathol. Exp. Neurol., 46: 419.PubMedCrossRefGoogle Scholar
- Pettegrew, J.W., Minshew, N.J., Cohen, M.M., Kopp, S•J., and Glonek, T., 1984, 31P NMR changes in Alzheimer’s and Huntington’s disease brain, Neurology, 34 (suppl 1 ): 281.Google Scholar