Culprit in Alzheimer's reverses paralysis in mice with multiple sclerosis

Washington, August 2 (ANI): A molecule blamed as the chief culprit in Alzheimer's disease unexpectedly reverses paralysis and inflammation in several distinct animal models with multiple sclerosis, researchers have found.

This surprising discovery comes on the heels of the recent failure of a large-scale clinical trial aimed at slowing the progression of Alzheimer's disease by attempting to clear the much-maligned molecule, known as A-beta, from Alzheimer's patients' bloodstreams.

While the findings are not necessarily applicable to the study of A-beta's role in the pathology of that disease, they may point to promising new avenues of treatment for multiple sclerosis.

A-beta is the chief component of the amyloid plaques that accumulate in the brains of Alzheimer's patients and serve as an identifying hallmark of the neurodegenerative disorder.

A-beta deposits also build up during the normal aging process and after brain injury. Concentrations of the peptide, along with those of the precursor protein from which it is carved, are found in multiple-sclerosis lesions as well, said the study's senior author Lawrence Steinman, MD, Stanford University School of Medicine.

In a lab dish, A-beta is injurious to many types of cells. And when it is administered directly to the brain, A-beta is highly inflammatory.

Yet little is known about the physiological role A-beta actually plays in Alzheimer's - or in MS, said Steinman, a professor of neurology and neurological sciences and of pediatrics and a noted multiple-sclerosis researcher. He, first author Jacqueline Grant, PhD, and their colleagues set out to determine that role in the latter disease.

Previous research by Steinman, who is also the George A. Zimmerman Professor, and others showed that both A-beta and its precursor protein are found in MS lesions. In fact, the presence of these molecules along an axon's myelinated coating is an excellent marker of damage there.

Given the peptide's nefarious reputation, Steinman and his associates figured that A-beta was probably involved in some foul play with respect to MS. To find out, they relied on a mouse model that mimics several features of multiple sclerosis - including the autoimmune attack on myelinated sections of the brain that causes MS.

Knowing that immunological events outside the brain can have such an effect within it, the Stanford scientists were keen on seeing what would happen when they administered A-beta by injecting it into a mouse's belly, rather than directly to the brain.

In mice whose immune systems had been "trained" to attack myelin, which typically results in paralysis, A-beta injections delivered before the onset of symptoms prevented or delayed the onset of paralysis. Even when the injections were given after the onset of symptoms, they significantly lessened the severity of, and in some cases reversed, the mice's paralysis.

Steinman repeated the experiment and got the same results.

The results proved that A-beta's moderating influence on the debilitating symptoms of the MS-like syndrome has nothing to do with A-beta's action within the brain itself, but instead is due to its effect on immune cells before they penetrate the brain.

Sophisticated laboratory tests showed that A-beta countered not only visible symptoms such as paralysis, but also the increase in certain inflammatory molecules that characterizes multiple-sclerosis flare-ups.

Inspection of the central nervous systems of the mice with the MS-resembling syndrome showed fewer MS-like lesions in the brains and spinal cords of treated mice than in those not given A-beta. There was also no sign of increased Alzheimer's-like plaques in the A-beta-treated animals.

"There probably is a multiple-sclerosis drug in all this somewhere down the line," Steinman said.

The results have been published online as the cover feature in Science Translational Medicine. (ANI)