Perspective:The Potential Roleof Circulating LysophosphatidylcholineinNeuroprotection againstAlzheimerDisease

Abstract

Alzheimerdisease(AD),themostcommoncauseofdementia,isaprogressivedisorderinvolvingcognitiveimpairment,lossoflearningandmemory, andneurodegenerationaffectingwideareasofthecerebralcortexandhippocampus.ADischaracterizedbyalteredlipidmetabolisminthebrain. Lower concentrations of long-chain PUFAs have been described in the frontal cortex, entorhinal cortex, and hippocampus in the brain in AD. The brain can synthesize only a few fatty acids; thus, most fatty acids must enter the brain from the blood. Recent studies show that PUFAs such as DHA(22:6)aretransportedacrosstheblood–brainbarrier(BBB)intheformoflysophosphatidylcholine(LPC)viaaspecificLPCreceptorattheBBB knownasthesodium-dependentLPCsymporter1(MFSD2A).HigherdietaryPUFAintakeisassociatedwithdecreasedriskofcognitivedeclineand dementiainobservationalstudies;however,PUFAsupplementation,withfattyacidsesterifiedintriacylglycerolsdidnotpreventcognitivedecline in clinical trials. Recent studies show that LPC is the preferred carrier of PUFAs across the BBB into the brain. An insufficient pool of circulating LPC containing long-chain fatty acids could potentially limit the supply of long-chain fatty acids to the brain, including PUFAs such as DHA, and play a role in the pathobiology of AD. Whether adults with low serum LPC concentrations are at greater risk of developing cognitive decline and AD remains a major gap in knowledge. Preventing and treating cognitive decline and the development of AD remain a major challenge. The LPC pathwayisapromisingareaforfutureinvestigatorstoidentifymodifiableriskfactorsforAD