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et al.
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Lysophosphatidylcholine as a preferred carrier form of docosahexaenoic acid to the brain
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2001
Maternal lipid levels across pregnancy impact the umbilical cord blood lipidome and infant birth weight
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Preferential incorporation of sn-2 lysoPC DHA over unesterified DHA in the young rat brain
F Thies
et al.
American Journal of Physiology
1994
Lysophosphatidylcholine as a carrier of docosahexaenoic acid to target tissues
M Lagarde
et al.
World Rev Nutr Diet
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Plasma BDNF is a more reliable biomarker than erythrocyte omega-3 index for the omega-3 fatty acid enrichment of brain
Dhavamani Sugasini
et al.
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Perspective: The Potential Role of Circulating Lysophosphatidylcholine in Neuroprotection against Alzheimer Disease
Richard D Semba
et al.
Advances in Nutrition
2020
Omega-3 PUFA metabolism and brain modifications during aging
Hillary Chappus-McCendie
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Prog Neuropsychopharmacol Biol Psychiatry
2019
Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease
Rhonda P Patrick
et al.
FASEB JOURNAL
2019
Carriers of an apolipoprotein E epsilon 4 allele are more vulnerable to a dietary deficiency in omega-3 fatty acids and cognitive decline
Tanya Gwendolyn Nock
et al.
Biochim Biophys Acta Mol Cell Biol Lipids.
2017
Docosahexaenoic acid prevents cognitive deficits in human apolipoprotein E epsilon 4-targeted replacement mice
Raphaël Chouinard-Watkins
et al.
Neurobiology of Aging
2017
Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent Suppression of Caveolae-Mediated Transcytosis
Benjamin J Andreone
et al.
Neuron
2017
Mechanisms of DHA transport to the brain and potential therapy to neurodegenerative diseases
Amanda Lo Van
et al.
Biochimie
2016
Enhanced incorporation of dietary DHA into lymph phospholipids by altering its molecular carrier
Papasani V Subbaiah
et al.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
2016
Mfsd2a-based pharmacological strategies for drug delivery across the blood-brain barrier
Jing-Zhang Wang
et al.
Pharmachological Research
2016
The Cellular and Molecular Landscapes of the Developing Human Central Nervous System
John C Silbereis
et al.
Neuron
2016
Efficient Docosahexaenoic Acid Uptake by the Brain from a Structured Phospholipid
Mayssa Hachem
et al.
Molecular Neurobiology
2015
A dose response randomised controlled trial of docosahexaenoic acid (DHA) in preterm infants.
C T Collins
et al.
Prostaglandins Leukot Essent Fatty Acids
2015
Blood-brain barrier: a dual life of MFSD2A?
Zhao Z
et al.
Neuron
2014
Pregnancy-induced metabolic phenotype variations in maternal plasma
Hemi Luan
et al.
Journal of Proteome Research
2014
MFSD2a, the Syncytin-2 receptor, is important for trophoblast fusion
C Toufaily
et al.
Placenta
2012
Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) - Implications for dietary recommendations
Philippe Guesnet
et al.
Biochimie
2011
Lipidomics reveals a remarkable diversity of lipids in human plasma
Oswald Quehenberger
et al.
J Lipid Res.
2010
DHA deficiency and prefrontal cortex neuropathology in recurrent affective disorders
Robert K McNamara
et al.
J Nutr.
2010
A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2
Cécile Esnault
et al.
Proc Natl Acad Sci USA
2008
The aging human orbitofrontal cortex: decreasing polyunsaturated fatty acid composition and associated increases in lipogenic gene expression and stearoyl-CoA desaturase activity
Robert K McNamara
et al.
Prostaglandins Leukot Essent Fatty Acids
2008
Cell survival matters: docosahexaenoic acid signaling, neuroprotection and photoreceptors
Nicolas G Bazan
et al.
Trends Neurosci
2006
The role of essential fatty acids in development
William C Heird
et al.
Annu Rev Nutr
2005
Essential fatty acid transfer and fetal development
S M Innis
et al.
Placenta
2005
Preferential transfer of 2-docosahexaenoyl-1-lysophosphatidylcholine through an in vitro blood-brain barrier over unesterified docosahexaenoic acid
N Bernoud
et al.
Journal of Neurochemistry
2002
The uptake and metabolism of plasma lysophosphatidylcholine in vivo by the brain of squirrel monkeys
D R Illingworth, O W Portman
et al.
Biochem J .
1972
Maternal DHA and the development of attention in infancy and toddlerhood
John Colombo
et al.
Child Dev.
2004
Daily Enteral DHA Supplementation Alleviates Deficiency in Premature Infants
Michelle L Baack
et al.
Lipids
2016
Adv Nutr . 2020 Jul 1;11(4):760-772. doi: 10.1093/advances/nmaa024.

Perspective: The Potential Role of Circulating Lysophosphatidylcholine in Neuroprotection against Alzheimer Disease

July 1, 2020
Richard D Semba

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

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.

Keywords
Cognition
LPC
DHA
EPA
Blood-brain barrier
Memory
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