Nerve cells communicate across the synaptic gap by releasing pulses of chemicals, and Cirrito's team found that these neurotransmitter spurts were accompanied by releases of amyloid-beta from the same area. The experiments not only established a likely neuronal storage locale and discharge mechanism for amyloid-beta, which goes on to wreak havoc in the intercellular spaces of the brain, they identified a probable cause for the protein's release in the synaptic activation itself. Although the discovery does not necessarily mean that heavy brain activity is to blame for Alzheimer's damage, it may explain why some of the most chronically active brain regions are also most severely affected in Alzheimer's patients.

One key to counteracting those effects is detecting the disease early, and another feat by Holtzman with Randall J. Bateman, also at the W.U. School of Medicine, should make that possible. They have devised a test that measures manufacture and disposal of amyloid-beta in the brain. The pair created a marked version of the amino acid leucine, which neurons normally use as a building block for the amyloid-beta protein, and then administered it to healthy young human subjects.

Bateman later looked for the appearance of a resulting marked amyloid-beta in the volunteers' spinal fluid and found that the protein was cleared slightly faster than it was made. The test could also be used on Alzheimer's sufferers, however, to help researchers resolve the longstanding question of whether the disease is caused by abnormally high amyloid-beta production or dysfunctional clearance of the protein. Eventually, the spinal-tap method could look for elevated amyloid-beta in people with early symptoms of suspected Alzheimer's or measure the effects of drug therapies on already-diagnosed patients.

One of those treatments might one day be based on a synthetic protein fragment Robert P. Hammer of Louisiana State University has developed to disrupt formation of the plaques believed to provoke massive brain cell death in Alzheimer's patients. The plaques are aggregations of fibers that form when individual amyloid-beta peptides begin abnormally sticking together. Hammer also tweaked building blocks of amyloid-beta, synthesizing a non-sticky version of the amino acids that permit amyloid-beta proteins to bind to each other. Adding the engineered fragments to a test tube of normal amyloid-beta blocked the proteins' ability to form fibers, even after four months' exposure. If it does the same in human brains, tens of millions of Alzheimer's sufferers might finally be liberated from a deadly burden of poisonous plaque.--Christine Soares

Beginning to See the Light

Two-dimensional light waves point toward optical imaging of viruses and the Invisible Man

Several years ago, electrical engineer Igor I. Smolyaninov deduced the properties of electromagnetic waves on a metal surface by applying the physics of time machines. The University of Maryland professor was studying what has become one of the sexiest areas of materials science: plasmonics, in which light is turned from a three-dimensional wave (a photon) into a two-dimensional one (a plasmon) rippling along, for example, the side of a metal sheet. If you put a droplet of liquid on the sheet, the plasmons can be trapped-just like photons inside a black hole. If you drill a hole through the sheet, the plasmons can travel from one side to the other-just like photons passing through a wormhole, a hypothetical passage between two different regions of spacetime. In fact, the hole might be used to create an analogue to a time machine and cause all the contradictions familiar to aficionados of science-fiction. Smolyaninov reasoned that if time machines do not work, then neither should their analogues, from which he drew conclusions about the behavior of the waves.

Smolyaninov and his colleagues have now used his liquid-droplet black-hole analogue to create a microscope that can see details smaller than the wavelength of the illuminating light-a feat that any physics textbook will tell you is impossible. The key is that plasmons have a shorter wavelength than the photons from which they were converted, so they respond to finer features. In one test, Smolyaninov's team used laser light with a wavelength of about 500 nanometers to generate plasmons with a wavelength of 70 nanometers. A drop of glycerin focused them to form a 2-D image, which a regular optical microscope viewed. The team took pictures of viruses 100 nanometers wide. The system is much easier to use than an electron microscope.

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