TY - JOUR
T1 - Altered SPMs and age-associated decrease in brain DHA in APOE4 female mice
AU - Martinsen, Anneloes
AU - Tejera, Noemi
AU - Vauzour, David
AU - Harden, Glenn
AU - Dick, James
AU - Shinde, Sujata
AU - Barden, Anne
AU - Mori, Trevor A.
AU - Minihane, Anne Marie
PY - 2019/9/1
Y1 - 2019/9/1
N2 - An apolipoprotein E (APOE) 4 genotype is the most important, common genetic determinant for Alzheimer disease (AD), and female APOE4 carriers present with an increased risk compared with males. The study quantified cortical and hippocampal fatty acid and phospholipid profiles along with select eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-derived specialized proresolving mediators (SPMs) in 2-, 9-, and 18-mo-old APOE3 and APOE4 male and female mice. A 10% lower cortical DHA was evident in APOE4 females at 18 mo compared with 2 mo, with no significant decrease in APOE3 or APOE4 males. This decrease was associated with a reduction in DHA-phosphatidylethanolamine. Older APOE4 females had a 15% higher oleic acid content compared with young mice. Although no sex*APOE genotype interactions were observed for SPMs expressed as a ratio of their parent compound, higher cortical 18R/S-hydroxy-5Z,8Z,11Z,14Z,16E-EPA, resolvin D3, protectin D1, 10S,17S-dihydroxy-4Z,7Z,11E,13E,15Z,19Z-DHA (10S,17S-diHDHA), maresin 1, 17S-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-DHA, and 14S-hydroxy-4Z,7Z,10Z,12E,16Z,19Z-DHA were evident in females, and lower cortical 17R-resolvin D1, 10S,17S-diHDHA, and 18-HEPE in APOE4. Our findings show a strong association between age, female sex, and an APOE4 genotype, with decreased cortical DHA and a number of SPMs, which together may contribute to the development of cognitive decline and AD pathology.-Martinsen, A., Tejera, N., Vauzour, D., Harden, G., Dick, J., Shinde, S., Barden, A., Mori, T. A., Minihane, A. M. Altered SPMs and age-associated decrease in brain DHA in APOE4 female mice.
AB - An apolipoprotein E (APOE) 4 genotype is the most important, common genetic determinant for Alzheimer disease (AD), and female APOE4 carriers present with an increased risk compared with males. The study quantified cortical and hippocampal fatty acid and phospholipid profiles along with select eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-derived specialized proresolving mediators (SPMs) in 2-, 9-, and 18-mo-old APOE3 and APOE4 male and female mice. A 10% lower cortical DHA was evident in APOE4 females at 18 mo compared with 2 mo, with no significant decrease in APOE3 or APOE4 males. This decrease was associated with a reduction in DHA-phosphatidylethanolamine. Older APOE4 females had a 15% higher oleic acid content compared with young mice. Although no sex*APOE genotype interactions were observed for SPMs expressed as a ratio of their parent compound, higher cortical 18R/S-hydroxy-5Z,8Z,11Z,14Z,16E-EPA, resolvin D3, protectin D1, 10S,17S-dihydroxy-4Z,7Z,11E,13E,15Z,19Z-DHA (10S,17S-diHDHA), maresin 1, 17S-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-DHA, and 14S-hydroxy-4Z,7Z,10Z,12E,16Z,19Z-DHA were evident in females, and lower cortical 17R-resolvin D1, 10S,17S-diHDHA, and 18-HEPE in APOE4. Our findings show a strong association between age, female sex, and an APOE4 genotype, with decreased cortical DHA and a number of SPMs, which together may contribute to the development of cognitive decline and AD pathology.-Martinsen, A., Tejera, N., Vauzour, D., Harden, G., Dick, J., Shinde, S., Barden, A., Mori, T. A., Minihane, A. M. Altered SPMs and age-associated decrease in brain DHA in APOE4 female mice.
KW - Alzheimer disease
KW - cortex
KW - fatty acids
KW - neuroinflammation
KW - specialized proresolving mediators
UR - http://www.scopus.com/inward/record.url?scp=85071785562&partnerID=8YFLogxK
U2 - 10.1096/fj.201900423R
DO - 10.1096/fj.201900423R
M3 - Article
C2 - 31251078
AN - SCOPUS:85071785562
SN - 0892-6638
VL - 33
SP - 10315
EP - 10326
JO - FASEB journal : official publication of the Federation of American Societies for Experimental Biology
JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology
IS - 9
ER -