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O4‐05‐04: ALTERED PLASMA PHOSPHOLIPID COMPOSITION IN AUTOSOMAL DOMINANT ALZHEIMER'S DISEASE: A DIAN STUDY
Author(s) -
Chatterjee Pratishtha,
Florence Lim Wei Ling,
Gupta Veer Bala,
Sohrabi Hamid R.,
Taddei Kevin,
Brown Belinda,
Masters Colin Louis,
Morris John Carl,
Martins Ralph
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.04.412
Subject(s) - phospholipid , lysophosphatidylcholine , phosphatidylcholine , pathogenesis , chemistry , biology , microbiology and biotechnology , medicine , biochemistry , membrane
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.