SERUM LONG-CHAIN N-3 FATTY ACID LEVELS ARE ASSOCIATED WITH PRESYNAPTIC PROTEINS IN THE HUMAN BRAIN

Abstract

Blood concentrations and intake of long chain n-3 polyunsaturated fatty acids (PUFAs) have been associated with cognitive decline and the development of dementia. Animal models suggest that one mechanism underlying this relation may be neuroprotection of n-3 PUFAs against loss in synaptic proteins. We report here the first human study to relate serum n-3 PUFA levels to brain tissue levels of presynaptic proteins. This study is based on 57 deceased participants of the Memory and Aging Project who underwent brain autopsy. Presynaptic protein concentrations in the brain and n-3 PUFA serum levels over a mean of 3.6 years with on average 2.7 biochemical assessments were determined. Brain concentrations of eight presynaptic proteins (complexin I and II, Sept5, SNAP-25, synaptophysin, synaptotagmin, syntaxin, and VAMP) were measured with monoclonal antibodies and ELISA techniques in 12 brain regions. Presynaptic protein levels for each region were log-transformed, standardized, and averaged across regions. Serum n-3 PUFA concentrations were averaged and determined in total ethanolamine plasmalogen (PL) and phosphatidylethanolamine (PE) by mass spectrometry. Linear regression models adjusting for age at death, sex and education level were used to assess the associations. In adjusted models PE docosahexaenoic acid (DHA) had linear associations with synaptophysin (β=1.18; SE=0.58, P=0.05), VAMP (β=1.03; SE=0.45, P=0.03), and SNAP-25 (β=1.20; SE=0.57, P=0.04) and marginal associations with syntaxin (β=1.09; SE=0.58, P=0.07) and Sept5 (β=0.85; SE=0.45, P=0.06). PL DHA showed significant associations with higher levels of complexin I and II (β=0.55; SE=0.22, P=0.02 and β=0.66; SE=0.28, P=0.02 respectively) and marginal associations with syntaxin (β=0.39; SE=0.22, P=0.09) and VAMP (β=0.34; SE=0.18, P=0.06). PL eicosapentaenoic acid (EPA) showed marginal linear associations with higher levels of synaptophysin (β=0.80; SE=0.43, P=0.07), synaptotagmin (β=0.68; SE=0.40, P=0.09), syntaxin (β=0.77; SE=0.43, P=0.08), VAMP (β=0.58; SE=0.34, P=0.10), SNAP-25 (β=0.73; SE=0.43, P=0.10), and Sept5 (β=0.63; SE=0.33, P=0.06). This study suggests that one potential biological mechanism underlying the relation of n-3 PUFAs, DHA in particular, to brain health during aging is maintenance of neural reserve by sustaining higher levels of presynaptic proteins.