title: Association between Plasma Ceramides and Phosphatidylcholines and Hippocampal Brain Volume in Late Onset Alzheimer's Disease.
abstract: Lipids such as ceramides and phosphatidylcholines (PC) have been found altered in the plasma of Alzheimer's disease (AD) patients in a number of discovery studies. For this reason, the levels of 6 ceramides and 3 PCs, with different fatty acid length and saturation levels, were measured in the plasma from 412 participants (AD n = 205, Control n = 207) using mass spectrometry coupled with ultra-performance liquid chromatography. After this, associations with AD status, brain atrophy, and age-related effects were studied. In the plasma of AD participants, cross-sectional analysis revealed elevated levels of three ceramides (Cer16:0 p < 0.01, Cer18:0 p < 0.01, Cer24:1 p < 0.05). In addition, two PCs in AD plasma (PC36:5 p < 0.05, PC38:6 p < 0.05) were found to be depleted compared to the control group, with PC36:5 also associating with hippocampal atrophy (p < 0.01). Age-specific analysis further revealed that levels of Cer16:0, Cer18:0, and Cer20:0 were associated with hippocampal atrophy only in younger participants (age < 75, p < 0.05), while all 3 PCs did so in the older participants (age > 75, p < 0.05). PC36:5 was associated with AD status in the younger group (p < 0.01), while PC38:6 and 40:6 did so in the older group (p < 0.05). In this study, elevated ceramides and depleted PCs were found in the plasma from 205 AD volunteers. Our findings also suggest that dysregulation in PC and ceramide metabolism could be occurring in different stages of AD progression.
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, UK.
authors.forename: Min
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Alejo
authors.initials: A
authors.lastname: Nevado-Holgado
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Whiley
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, UK.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Snowden
authors.affiliation: Department of Neurology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.affiliation: Department of Old Age Psychiatry & Psychotic Disorders, Medical University of Lodz, Lodz, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Kloszewska
authors.affiliation: Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
authors.affiliation: Third Department of Neurology, Memory and Dementia Centre, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: Department of Internal and Geriatrics Medicine, INSERM U 1027, Gerontopole, Hôpitaux de Toulouse, Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.affiliation: Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Madhav
authors.initials: M
authors.lastname: Thambisetty
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: Richard J B
authors.initials: RJB
authors.lastname: Dobson
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: John F
authors.initials: JF
authors.lastname: Powell
authors.affiliation: Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Lupton
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.|National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) for Mental Health at South London and Maudsley NHS Foundation Trust, UK.
authors.forename: Andy
authors.initials: A
authors.lastname: Simmons
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: Latha
authors.initials: L
authors.lastname: Velayudhan
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: Petroula
authors.initials: P
authors.lastname: Proitsi
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Legido-Quigley
mesh_terms: D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000000981:diagnostic imaging* / Q000473:pathology; D001284:Atrophy; D015415:Biomarkers / Q000097:blood; D002518:Ceramides / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D010713:Phosphatidylcholines / Q000097:blood*
chemical_list: D015415:Biomarkers; D002518:Ceramides; D010713:Phosphatidylcholines
keywords: Alzheimer’s disease; brain atrophy; ceramide; phosphatidylcholine