APOE ε4 specific imbalance of arachidonic acid and docosahexaenoic acid in serum phospholipids identifies individuals with preclinical Mild Cognitive Impairment/Alzheimer's Disease.
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.
Roskamp Institute, Sarasota, FL 34234, USA.
Laila
L
Abdullah
Roskamp Institute, Sarasota, FL 34234, USA.
James E
JE
Evans
Roskamp Institute, Sarasota, FL 34234, USA.
Tanja
T
Emmerich
Roskamp Institute, Sarasota, FL 34234, USA.
Gogce
G
Crynen
Roskamp Institute, Sarasota, FL 34234, USA.
Ben
B
Shackleton
Roskamp Institute, Sarasota, FL 34234, USA.
Andrew P
AP
Keegan
Roskamp Institute, Sarasota, FL 34234, USA.
Cheryl
C
Luis
University of Illinois at Chicago, Chicago, IL 60607, USA.
Leon
L
Tai
University of Illinois at Chicago, Chicago, IL 60607, USA.
Mary J
MJ
LaDu
Roskamp Institute, Sarasota, FL 34234, USA.
Michael
M
Mullan
Roskamp Institute, Sarasota, FL 34234, USA.
Fiona
F
Crawford
Roskamp Institute, Sarasota, FL 34234, USA.
Corbin
C
Bachmeier
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis*; D000818:Animals; D053327:Apolipoprotein E4 / Q000097:blood*; D016718:Arachidonic Acid / Q000097:blood*; D060825:Cognitive Dysfunction / Q000097:blood / Q000175:diagnosis*; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice
D053327:Apolipoprotein E4; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid
Alzheimer’s disease; arachidonic acid; docosahexaenoic acid; lipidomics; phospholipid