Nutrients required for phospholipid synthesis are lower in blood and cerebrospinal fluid in mild cognitive impairment and Alzheimer's disease dementia

Abstract Introduction Synaptic membrane formation depends on nutrients that fuel metabolic pathways for the synthesis of constituent phospholipids. Consequently, insufficient availability of such nutrients may restrict membrane formation and contribute to synaptic dysfunction in Alzheimer's disease (AD). We assessed whether blood and cerebrospinal fluid (CSF) concentrations of nutrients related to phospholipid synthesis differ among patients with AD, mild cognitive impairment (MCI), and control subjects. Methods Concentrations of uridine, choline, folate, homocysteine, and other related metabolites were analyzed in paired blood and CSF samples from subjects selected from the Amsterdam Dementia Cohort with AD ( n  = 150; age, 66 ± 7 years; 37% female), MCI ( n  = 148; age, 66 ± 8 years; 37% female), and control subjects ( n  = 148; age, 59 ± 8 years; 38% female). Results Age- and gender-adjusted analysis of variance revealed different concentrations of circulating uridine, choline, and folate and CSF uridine, folate, and homocysteine (all P P Discussion AD and MCI patients have lower levels of nutrients involved in phospholipid synthesis. The current observations warrant exploration of the application of nutritional strategies in the early stages of AD.