Glitter from silver lights up Alzheimer’s dark secrets

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The picture shows toxic Alzheimer's amyloid beta molecules landing on a fake cell membrane, wrapped around a silver nanoparticle. A laser, with help from the silver particle, lights up the molecule to reveal its structure. Credit: Copyright Debanjan Bhowmik; Credit to Debanjan Bhowmik, TIFR, Mumbai

The picture shows toxic Alzheimer’s amyloid beta molecules landing on a fake cell membrane, wrapped around a silver nanoparticle. A laser, with help from the silver particle, lights up the molecule to reveal its structure. Credit: Copyright Debanjan Bhowmik; Credit to Debanjan Bhowmik, TIFR, Mumbai

The elusive toxic form of the Alzheimer’s molecule has now been observed, during its attempt to bore into the outer covering of a cell decoy, using a new method involving laser light and fat-coated silver nanoparticles.

“Everybody wants to make the key to solve Alzheimer’s Disease, but we don’t know what the lock looks like. We now have a glimpse of something which could be the lock. May be it’s still not the real thing, but as of now, this is our best bet,” says Sudipta Maiti, who co-directed the efforts with P. K. Madhu (both from TIFR). If they are right, then designing the key, i.e. a drug molecule which can attack the lock, may be more achievable now.

The lock looks like a bunch of amyloid beta molecules in the shape of a hairpin, but with a twist ie beta-hairpin.. This may allow these bunch of amyloid beta molecules to form toxic pores in the cell membranes.”

They studied a tiny laser-induced signal from the amyloid beta which reported their shape. A critical modification in the original Raman Spectroscopy technique allowed the measurement of tiny signals that would otherwise have gone unnoticed. They encased silver nanoparticles in a fat layer (“membrane”) that mimicked the outer membranes of living cells. According to co-author Gilbert Walker, “While the amyloid beta got fooled by it and stuck to the membrane, the silver inside enhanced the signal to a measurable level and acted as a light beacon to reveal the peptide signature.” The technique offers promise for deciphering the shape of many such membrane molecules, some of which may be related to other types of diseases. http://www.eurekalert.org/pub_releases/2015-08/tiof-gfs082515.php

http://dx.doi.org/10.1021/acsnano.5b03175