Wurtman RJ, Ulus IH, Cansev M, Watkins CJ, Wang L, Marzloff G.
Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally.
Brain Res. 2006 May 9;1088(1):83-92.
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With several publications already showing an intrinsic link between APP processing and lipids—in addition to the well-established impact lipids can have on neuronal function—dietary approaches are highly interesting for therapy and AD prevention. Though their impact is likely to be moderate only, they come with few side effects and are likely to be well tolerated in combination with pharmaceutical treatments. With respect to lipid consumption, docosahexaenoic acid (DHA) is hot on the list. While DHA is not a component of the standard chow given to gerbils—the animals used in this study—in humans it is, or better put, it should be.
Though AD is not directly addressed in this paper, it presents some data which are very germane to the disease. The central idea this publication puts forward is that uridine or other pyrimidines strongly enhance the effect DHA has on synaptic quantity, basically by allowing more DHA-containing lipids to be synthesized in the brain. This is certainly important information when it comes to the design of health-targeted dietary supplements for the elderly (and general) population.
Often such experiments are performed by formulating an all-in-one diet. This is a convenient and promising approach to maximize the potential effect on brain function, but it leaves follow-up studies with little clue as to which of the ingredients were active and which, if any, of the substances had synergistic effects with other substances. But Wurtman et al. compared what happens if DHA is fed to the animals in the presence of other molecules needed to build certain phospholipids. The answer is clear-cut: after only 4 weeks of treatment, levels of synaptic (synapsin-1 and PSD-95) and neuritic proteins increased, and DHA became very efficiently incorporated.
Most significant across the board was the increase in sphingomyelin, another lipid that is especially enriched in brain. A comparable increase of sphingomyelin in cultured cells is known to result in drastically reduced Aβ production. Although there are other ways in which DHA might down-regulate Aβ production (e.g., via cholesterol compartmentalization, raft composition etc.), this unexpectedly strong increase in sphingomyelin certainly adds to the portfolio of mechanistic explanations. While cell culture studies cannot be compared with animal studies, it would be interesting to see how such a diet affects gerbils or transgenic AD mice (although the gerbil is, in some aspects of particular relevance to this study, closer to the human).
In summary, this (or similar) combination diet smells like it might be ripe for AD prevention, provided, of course, that future studies can show that the diets lower Aβ.