Methylxanthines Induce a Change in the AD/Neurodegeneration-Linked Lipid Profile in Neuroblastoma Cells

Alzheimer's disease (AD) is characterized by an increased plaque burden and tangle accumulation in the brain accompanied by extensive lipid alterations. Methylxanthines (MTXs) are alkaloids frequently consumed by dietary intake known to interfere with the molecular mechanisms leading to AD. Besides the fact that MTX consumption is associated with changes in triglycerides and cholesterol in serum and liver, little is known about the effect of MTXs on other lipid classes, which raises the question of whether MTX can alter lipids in a way that may be relevant in AD. Here we have analyzed naturally occurring MTXs caffeine, theobromine, theophylline, and the synthetic MTXs pentoxifylline and propentofylline also used as drugs in different neuroblastoma cell lines. Our results show that lipid alterations are not limited to triglycerides and cholesterol in the liver and serum, but also include changes in sphingomyelins, ceramides, phosphatidylcholine, and plasmalogens in neuroblastoma cells. These changes comprise alterations known to be beneficial, but also adverse effects regarding AD were observed. Our results give an additional perspective of the complex link between MTX and AD, and suggest combining MTX with a lipid-altering diet compensating the adverse effects of MTX rather than using MTX alone to prevent or treat AD.

Automated summary

Alzheimer's disease is characterized by increased plaque formation and tangle accumulation in the brain, along with extensive lipid alterations. Methylxanthines, a type of alkaloid commonly consumed through diet, have been found to interfere with the molecular mechanisms leading to Alzheimer's disease. Our study shows that methylxanthines not only affect triglycerides and cholesterol in the liver and serum, but also induce changes in other lipid classes in neuroblastoma cells. These changes include both beneficial and adverse effects related to Alzheimer's disease. Therefore, we suggest combining methylxanthines with a diet that alters lipid metabolism to counteract the adverse effects.