Perspective: The potential role of circulating lysophosphatidylcholine in neuroprotection against alzheimer disease

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Alzheimer disease (AD), the most common cause of dementia, is a progressive disorder involving cognitive impairment, loss of learning and memory, and neurodegeneration affecting wide areas of the cerebral cortex and hippocampus. AD is characterized by altered lipid metabolism in the brain. 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) are transported across the blood-brain barrier (BBB) in the form of lysophosphatidylcholine (LPC) via a specific LPC receptor at the BBB known as the sodium-dependent LPC symporter 1 (MFSD2A). Higher dietary PUFA intake is associated with decreased risk of cognitive decline and dementia in observational studies; however, PUFA supplementation, with fatty acids esterified in triacylglycerols did not prevent cognitive decline 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 pathway is a promising area for future investigators to identify modifiable risk factors for AD.

Original languageEnglish (US)
Pages (from-to)760-772
Number of pages13
JournalAdvances in Nutrition
Issue number4
StatePublished - 2020


  • Alzheimer disease
  • Blood-brain barrier
  • Cognition
  • Dementia
  • Docosahexaenoic acid
  • Lysophosphatidylcholine
  • Polyunsaturated fatty acid

ASJC Scopus subject areas

  • Food Science
  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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