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J Alzheimers Dis. 2016;50(3):887-94. doi: 10.3233/JAD-150948.

Plasma Phospholipid and Sphingolipid Alterations in Presenilin1 Mutation Carriers: A Pilot Study.

Chatterjee P1,2,3,4, Lim WL2,3,4, Shui G5, Gupta VB2,3,4, James I6, Fagan AM7,8, Xiong C8,9, Sohrabi HR1,2,3,4, Taddei K1,2,4, Brown BM1,2,4, Benzinger T8,10, Masters C11, Snowden SG12, Wenk MR13, Bateman RJ7,8, Morris JC7,8, Martins RN1,2,3,4.

Author information

1
School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia.
2
The McCusker Alzheimer's Research Foundation, Perth, WA, Australia.
3
The CRC for Mental Health, Australia.
4
School of Medical Sciences, Edith Cowan University, Perth, WA, Australia.
5
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
6
Institute for Immunology and Infectious diseases, Murdoch University, Perth, WA, Australia.
7
Department of Neurology, Washington University, St. Louis, MO, USA.
8
Knight Alzheimer's Disease Research Center, Washington University, St. Louis, MO, USA.
9
Division of Biostatistics, Washington University, St. Louis, MO, USA.
10
Department of Radiology, Washington University, St. Louis, MO, USA.
11
The Mental Health Research Institute, University of Melbourne, Melbourne, VA, Australia.
12
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
13
Department of Biochemistry and Department of Biological Sciences, National University of Singapore, Singapore.

Abstract

BACKGROUND AND 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).

CONCLUSION:

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.

KEYWORDS:

Alzheimer’s disease; biomarkers; familial Alzheimer’s disease; phospholipids; sphingolipids

PMID:
26836186
PMCID:
PMC4943576
DOI:
10.3233/JAD-150948
[Indexed for MEDLINE]
Free PMC Article

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