Alzheimer's Disease Research - Current Award

	Wolfgang Quitschke, Ph.D. State University of New York at Stony Brook Stony Brook, NY Title: Effect Of Serum-Solubilized Curcumin On Plaques In Alzheimer’s Disease Transgenic Mice Non-Technical Title: Effect Of Injectable Derivatives Of The Turmeric Spice On Plaques In AD Transgenic Mice Duration: April 1, 2009 - March 31, 2012 Award Type: Pilot Award Amount: $104,762
Summary: Experimentally, curcumin (turmeric spice) has been implicated in resolving and preventing Alzheimer’s disease associated plaques or deposits both in living systems and in test tubes. Epidemiological data suggest that the consumption of curcumin is linked to a lower incidence of Alzheimer’s disease. However, the solubility of curcumin in watery solutions is exceedingly low, which limits its systemic absorption and therapeutic potential. A new method is proposed to treat or prevent amyloid plaque formation associated with Alzheimer’s disease by injection of highly concentrated blood serum-solubilized curcumin.

Details:

Our previous research has largely been focused on investigating the regulation of genes associated with Alzheimer’s disease. However, upon learning about the epidemiological link between a lower incidence of Alzheimer disease and the consumption of the spice turmeric, I became interested in the compound curcumin, which is an active ingredient in turmeric. Upon attempting to expose cultured cells to curcumin, I became aware of the technical problems in solubilizing the compound and measuring its concentration. In over 2,000 publications about this compound, the issue of solubility was never or rarely addressed. Hence, I proceeded to develop a novel method to solubilize curcumin in blood serum and to reliably measure its concentration. The concentration of curcumin achieved in serum is at least 1,000-fold higher than the concentration necessary to resolve or prevent deposits associated with Alzheimer’s disease. Therefore, the serum-solubilized curcumin lends itself to therapeutic application by intravenous injection of small amounts of serum derived from the patient's own blood. Using the patient's own serum prevents the transmission of blood-borne diseases and potential immunological reactions. The feasibility of such a treatment option will be investigated in this proposal. For this purpose transgenic mice will be used that have been designed to develop Alzheimer’s disease associated plaques. The proposal will specifically address the following questions:

1. How does the injection of curcumin-enriched serum affect its bioavailability?
2. Can such injected serum prevent plaque formation in mice?
3. Can injected serum-solubilized curcumin resolve preexisting plaques in transgenic mice?

Progress Updates:

The goal of this proposal is to investigate the effect of curcumin-enriched serum on plaque formation in the brains of mice that have a disease similar to human Alzheimer’s disease (AD). Curcumin is a natural component of the spice, turmeric. Blood will be withdrawn from many different mice and the serum (the cell-free liquid portion of blood) will be experimentally enriched with curcumin. The curcumin-enriched serum will be injected into the AD mice. Particular attention will be paid to the ability of curcumin to prevent plaque formation and eliminate existing plaques. The experiments will be carried out in a manner that mimics a potential human serum delivery method, thus providing a possible treatment for AD.

Before studies could begin in mice, preliminary studies in rats (a breed called Sprague Dawley) were necessary to establish the feasibility of the project, primarily with regard to tolerability of the injected curcumin-enriched serum. Rat serum was obtained from commercial sources and enriched with curcumin. Small volumes of this mixture (2.5 milliliters) were injected once per week either intravenously (directly in the blood stream) or subcutaneously (just under the skin) into the Sprague Dawley rats. In the case of intravenous injection, this represented approximately 5% of the total blood volume. In both cases, no negative results on the well-being of the rats were observed. Particular concerns were that curcumin might have toxic effects or that the injected serum might induce allergic reactions. However, no such adverse effects were detected during regular weekly injections for a period exceeding six months.

These results establish the protocol for upcoming injections into AD mice that are designed to establish whether injected serum-solubilized curcumin can prevent or reverse plaques associated with AD. With this proposed delivery system, initial serum concentrations of curcumin are achieved that are up to a 1000-fold higher than can possibly be obtained by oral intake. Should these experiments prove successful, a human application would be of unprecedented benefit for either preventing Alzheimer’s disease plaque formation or possibly reverse existing plaques.