title: Plasma Phospholipid and Sphingolipid Alterations in Presenilin1 Mutation Carriers: A Pilot Study.
abstract: OBJECTIVE
  Aberrant lipid metabolism has been implicated in sporadic Alzheimer's disease (AD). The current study investigated plasma phospholipid and sphingolipid profiles in individuals carrying PSEN1 mutations responsible for autosomal dominant AD (ADAD).
  
  
  METHODS
  Study participants evaluated were from the Perth and Melbourne sites of the Dominantly Inherited Alzheimer Network (DIAN) study. Plasma phospholipid and sphingolipid profiles were measured using liquid chromatography coupled with mass spectrometry in 20 PSEN1 mutation carriers (MC; eight of whom were symptomatic and twelve asymptomatic, based on Clinical Dementia Rating scores) and compared with six non carriers (NC) using linear mixed models. Further, AD gold standard biomarker data obtained from the DIAN database were correlated with lipid species significantly altered between MC and NC, using Spearman's correlation coefficient.
  
  
  RESULTS
  One-hundred and thirty-nine plasma phospholipid and sphingolipid species were measured. Significantly altered species in MC compared to NC primarily belonged to choline and ethanolamine containing phospholipid classes and ceramides. Further phosphatidylcholine species (34:6, 36:5, 40:6) correlated with cerebrospinal fluid tau (p <  0.05), and plasmalogen ethanolamine species (34:2, 36:,4) correlated with both cerebrospinal fluid tau and brain amyloid load within the MC group (p <  0.05).
  
  
  CONCLUSIONS
  These findings indicate altered phospholipid and sphingolipid metabolism in ADAD and provide insight into the pathomolecular changes occurring with ADAD pathogenesis. Further, findings reported in this study allow comparison of lipid alterations in ADAD with those reported previously in sporadic AD. The findings observed in the current pilot study warrant validation in the larger DIAN cohort.
authors.affiliation: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia.|The McCusker Alzheimer's Research Foundation, Perth, WA, Australia.|The CRC for Mental Health, Australia.|School of Medical Sciences, Edith Cowan University, Perth, WA, Australia.
authors.forename: Pratishtha
authors.initials: P
authors.lastname: Chatterjee
authors.affiliation: The McCusker Alzheimer's Research Foundation, Perth, WA, Australia.|The CRC for Mental Health, Australia.|School of Medical Sciences, Edith Cowan University, Perth, WA, Australia.
authors.forename: Wei L F
authors.initials: WL
authors.lastname: Lim
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.affiliation: The McCusker Alzheimer's Research Foundation, Perth, WA, Australia.|The CRC for Mental Health, Australia.|School of Medical Sciences, Edith Cowan University, Perth, WA, Australia.
authors.forename: Veer B
authors.initials: VB
authors.lastname: Gupta
authors.affiliation: Institute for Immunology and Infectious diseases, Murdoch University, Perth, WA, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: James
authors.affiliation: Department of Neurology, Washington University, St. Louis, MO, USA.|Knight Alzheimer's Disease Research Center, Washington University, St. Louis, MO, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University, St. Louis, MO, USA.|Division of Biostatistics, Washington University, St. Louis, MO, USA.
authors.forename: Chengjie
authors.initials: C
authors.lastname: Xiong
authors.affiliation: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia.|The McCusker Alzheimer's Research Foundation, Perth, WA, Australia.|The CRC for Mental Health, Australia.|School of Medical Sciences, Edith Cowan University, Perth, WA, Australia.
authors.forename: Hamid R
authors.initials: HR
authors.lastname: Sohrabi
authors.affiliation: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia.|The McCusker Alzheimer's Research Foundation, Perth, WA, Australia.|School of Medical Sciences, Edith Cowan University, Perth, WA, Australia.
authors.forename: Kevin
authors.initials: K
authors.lastname: Taddei
authors.affiliation: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia.|The McCusker Alzheimer's Research Foundation, Perth, WA, Australia.|School of Medical Sciences, Edith Cowan University, Perth, WA, Australia.
authors.forename: Belinda M
authors.initials: BM
authors.lastname: Brown
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University, St. Louis, MO, USA.|Department of Radiology, Washington University, St. Louis, MO, USA.
authors.forename: Tammie
authors.initials: T
authors.lastname: Benzinger
authors.affiliation: The Mental Health Research Institute, University of Melbourne, Melbourne, VA, Australia.
authors.forename: Colin
authors.initials: C
authors.lastname: Masters
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Snowden
authors.affiliation: Department of Biochemistry and Department of Biological Sciences, National University of Singapore, Singapore.
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Wenk
authors.affiliation: Department of Neurology, Washington University, St. Louis, MO, USA.|Knight Alzheimer's Disease Research Center, Washington University, St. Louis, MO, USA.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Bateman
authors.affiliation: Department of Neurology, Washington University, St. Louis, MO, USA.|Knight Alzheimer's Disease Research Center, Washington University, St. Louis, MO, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia.|The McCusker Alzheimer's Research Foundation, Perth, WA, Australia.|The CRC for Mental Health, Australia.|School of Medical Sciences, Edith Cowan University, Perth, WA, Australia.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010743:Phospholipids / Q000097:blood*; D010865:Pilot Projects; D053764:Presenilin-1 / Q000235:genetics*; D013107:Sphingolipids / Q000097:blood*
chemical_list: D001057:Apolipoproteins E; D010743:Phospholipids; D053764:Presenilin-1; D013107:Sphingolipids
keywords: Alzheimer’s disease; biomarkers; familial Alzheimer’s disease; phospholipids; sphingolipids
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