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

Abstract

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 SyndromeCholinergic NeuronSenile PlaqueDown Syndrome PatientCholinergic DeficitThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.