Background: Altered phospholipid metabolism has been reported in sporadic Alzheimer’s disease (AD). This study investigated phospholipid alterations in the cerebrospinal fluid (CSF) of asymptomatic and symptomatic individuals carrying a Presenilin1 mutation responsible for autosomal dominant AD (mutation carriers; MC). The study allows monitoring phospholipid alterations with symptomatic disease progression, thus providing insight into mechanisms associated with AD pathogenesis, and enabling the identification of candidate phospholipids as potential diagnostic biomarkers. Methods: Participants were recruited from the Perth and Melbourne sites of the multicentre Dominantly Inherited Alzheimer Network (DIAN) study. Based on Clinical Dementia Rating (CDR) scores, participants were classified as asymptomatic (CDR=0) and symptomatic (CDR>0). The CSF profiles of eleven asymptomatic MC were compared with six symptomatic MC. CSF phospholipids were extracted using the modified Bligh and Dyer method and analysed on the QTRAP 4000 mass spectrometer coupled to a HPLC system using the multiple reaction monitoring method. Results: The present study measured eighty-six lipid species from the sphingolipid and choline containing phospholipid classes. Phospholipid species primarily from the lysophosphatidylcholine group were significantly increased (p<0.05) while sulfatide species were significantly decreased (p<0.05), in symptomatic MC compared to asymptomatic MC. Conclusions: Increased lysophosphatidylcholine may indicate increased inflammation and Phospholipase A2 activity with symptomatic disease progression; while decreased sulfatide levels with symptomatic disease progression indicate neuronal dysfunction, given their role in several biological processes (Vos JP, 1994). Phospholipids and sphingolipids observed to be significantly altered in the current study will need to be extended and validated in the greater DIAN cohort comprising all DIAN study sites.
|Number of pages||1|
|Journal||Alzheimer's and Dementia|
|Issue number||7 Supplement|
|Publication status||Published - 2015|
|Event||Alzheimer's Association International Conference 2015 - Washington, United States|
Duration: 18 Jul 2015 → 23 Jul 2015