Research Paper Volume 9, Issue 3 pp 964—985

APOE ε4 specific imbalance of arachidonic acid and docosahexaenoic acid in serum phospholipids identifies individuals with preclinical Mild Cognitive Impairment/Alzheimer’s Disease

Laila Abdullah1, , James E. Evans1, , Tanja Emmerich1, , Gogce Crynen1, , Ben Shackleton1, , Andrew P. Keegan1, , Cheryl Luis1, , Leon Tai2, , Mary J. LaDu2, , Michael Mullan1, , Fiona Crawford1, , Corbin Bachmeier1, ,

  • 1 Roskamp Institute, Sarasota, FL 34234, USA
  • 2 University of Illinois at Chicago, Chicago, IL 60607, USA

Received: November 21, 2016       Accepted: March 11, 2017       Published: March 23, 2017
How to Cite

Copyright: © 2017 Abdullah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


This study was designed to explore the influence of apolipoprotein E (APOE) on blood phospholipids (PL) in predicting preclinical Alzheimer’s disease (AD). Lipidomic analyses were also performed on blood from an AD mouse model expressing human APOE isoforms (EFAD) and five AD mutations and from 195 cognitively normal participants, 23 of who converted to mild cognitive impairment (MCI)/AD within 3 years. APOE ε4-carriers converting to MCI/AD had high arachidonic acid (AA)/docosahexaenoic acid (DHA) ratios in PL compared to cognitively normal ε4 and non-ε4 carriers. Arachidonic acid and DHA containing PL species, ε4-status and Aβ42/Aβ40 ratios provided 91% accuracy in detecting MCI/AD. Fish oil/omega-3 fatty acid consumption was associated with lower AA/DHA ratios even among ε4 carriers. High plasma AA/DHA ratios were observed in E4FAD compared to EFAD mice with other isoforms. In particular, alterations in plasma AA and DHA containing PL species were also observed in the brains of E4FAD mice compared to E3FAD mice. Despite the small sample size and a short follow-up, these results suggest that blood PL could potentially serve as biomarkers of preclinical MCI/AD.


AD: Alzheimer’s disease; MCI: mild cognitive impairment; PL: phospholipid; PC: phosphatidylcholine; PE: phosphatidylethanolamine; PI: phosphatidylinositol; LPC: lyso-phosphatidylcholine; ROC: receiver operator curves.