Altered plasma phospholipid composition in autosomal dominant Alzheimer's disease: a DIAN study

Pratishtha Chatterjee, Wei Ling Florence Lim, Veer Bala Gupta, Hamid R. Sohrabi, Kevin Taddei, Belinda Brown, Colin Louis Masters, John Carl Morris, Ralph Martins

    Research output: Contribution to journalMeeting abstractpeer-review


    Background: Currently post-mortem autopsy is the only definitive diagnosis for Alzheimer's disease (AD), while pre-mortem biomarkers in the cerebrospinal fluid and neuroimaging are invasive and uneconomical. This study compares plasma phospholipid profiles in individuals destined to develop AD (carry a mutation responsible for autosomal dominant AD; MC) with those who are non-carriers of the mutations (NC). In addition to providing insight into the pathogenesis of AD, this study allows monitoring of pathogenic phospholipid changes several years before the onset of AD; thus enabling identification of candidate phospholipids as potential diagnostic biomarkers. Methods: Participants belonged to Perth and Melbourne sites of the multicentre Dominantly Inherited Alzheimer Network (DIAN) study. The plasma phospholipid profiles of twenty-eight mutation carriers were compared against sixteen non-carriers. Plasma phospholipids were extracted by the modified Bligh and Dyer method and run on a QTRAP 4000 mass spectrometer via targeted flow injection using multiple reaction monitoring method. Results: Two-hundred and forty phospholipid species were detected, belonging to six major phospholipid classes. Phospholipid species primarily belonging to the lysophosphatidylcholine group were significantly increased in mutation carriers compared to non-carriers (p<0.05). Conclusions: Increased lysophosphatidylcholine in AD pathology corroborate previous reports on altered phosphatidylcholine metabolism in AD brain (Nitsch RM, 1992) and decreased plasma phosphatidylcholine levels (Whiley L, 2014). Phospholipids observed to be significantly altered between MC and NC need to be validated with liquid chromatography coupled with mass spectrometry.
    Original languageEnglish
    Article numberO4-05-04
    Pages (from-to)P260
    Number of pages1
    JournalAlzheimer's and Dementia
    Issue number4 Supplement
    Publication statusPublished - 2014
    EventAlzheimer's Association International Conference 2014 - Copenhagen, Denmark
    Duration: 12 Jul 201417 Jul 2014


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