The effects of methylene blue will be difficult to sort out because it is so pleiotropic. One downside of its use in AD is that it impairs microtubule assembly, as described in a new study that is now available online (Crowe et al.,, 2009, in press).

References:
Crowe A, Huang W, Ballatore C, Johnson RL, Hogan AM, Huang R, Wichtermann J, McCoy J, Huryn DM, Auld DS, Smith Iii AB, Inglese J, Trojanowski JQ, Austin CP, Brunden KR, Lee VM. The Identification of Aminothienopyridazine Inhibitors of Tau Assembly by Quantitative High-Throughput Screening. Biochem, In press, 2009

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It has been known for about 130 years that methylene blue, either injected in vivo or applied to freshly removed or cultured tissue, is decolorized (reduced to leuco-MB), and taken up rather selectively by axons of neurons, in which it can be made visible by reoxidation. For this vital staining, it can be advantageous for some purposes to use the leuco-dye.

Some drugs (notably ouabain, which blocks Na/K-ATPase) inhibit vital staining of neurons by methylene blue. The dye crosses the blood-brain barrier, perhaps as the hydrophobic leuco-dye. The entry of organic compounds (such as vital stains and drugs) into cells is largely determined by physicochemical properties (QSAR) that are partly predictable from the structural formulas.

The online article does not address the matter of how methylene blue or its leuco-dye might inhibit the undesirable aggregation of tau, huntingtin, etc. The clinical trial doses of the dye are very small.

Physicians and surgeons regularly use much larger single doses for diagnostic purposes. They use methylene blue chloride (approved in the...  Read more

It has been known for about 130 years that methylene blue, either injected in vivo or applied to freshly removed or cultured tissue, is decolorized (reduced to leuco-MB), and taken up rather selectively by axons of neurons, in which it can be made visible by reoxidation. For this vital staining, it can be advantageous for some purposes to use the leuco-dye.

Some drugs (notably ouabain, which blocks Na/K-ATPase) inhibit vital staining of neurons by methylene blue. The dye crosses the blood-brain barrier, perhaps as the hydrophobic leuco-dye. The entry of organic compounds (such as vital stains and drugs) into cells is largely determined by physicochemical properties (QSAR) that are partly predictable from the structural formulas.

The online article does not address the matter of how methylene blue or its leuco-dye might inhibit the undesirable aggregation of tau, huntingtin, etc. The clinical trial doses of the dye are very small.

Physicians and surgeons regularly use much larger single doses for diagnostic purposes. They use methylene blue chloride (approved in the BP, USP, etc.), not the cheaper zinc chloride double-salt that has various industrial uses. The simple chloride is the only salt of methylene blue that can be certified by the Biological Stain Commission, for testing milk, coloring dead organisms or tissues, and inclusion in stains for blood cells and malaria parasites.

References:
Kiernan JA. Effects of metabolic inhibitors on vital staining with methylene blue. Histochemistry. 1974;40:51-57. Abstract

Horobin, R. W. & Kiernan, J. A. (eds) 2002. Conn's Biological Stains. A Handbook of Dyes and Fluorochromes for use in Biology and Medicine. 10th ed. Oxford & New York: BIOS-Springer. ISBN 1859960995

View all comments by John Kiernan