Three Steps Forward on Alzheimer's

It's been almost a century since Alois Alzheimer first found fibrous plaques infesting the brains of people with senile dementia, but scientists still don't know for sure how--or even if--the plaques cause Alzheimer's disease. Now, a trio of studies in the July issue of Nature Medicine opens new avenues for plaque research by presenting a new animal model for plaque formation, a diagnostic tool for spotting them, and a possible way to break them down.

Scientists have long suspected that Alzheimer's patients lose their memories and their wits when amyloid beta proteins form needlelike aggregates that punch holes in brain cells and kill them. Alzheimer's plagues primarily the elderly, but scientists haven't been able to figure out why because they lacked a good animal model of the disease; in earlier mouse models, amyloid plaques formed but the brain cells survived. Now neurologists Changiz Geula and Bruce Yankner of Harvard Medical School have found such a model: Rhesus monkeys. They injected tiny amounts of amyloid protein into the brains of the monkeys and found that old Rhesus monkeys developed Alzheimer's-like symptoms but young monkeys stayed healthy.

Research on plaques has also been hampered by the lack of a good method for diagnosing Alzheimer's disease in living patients. A new diagnostic test, created by Detlev Riesner and colleagues at the Heinrich-Heine-Universitat in Dusseldorf, Germany, may help spot the plaques long before brain cells die off. The test, which measures beta amyloid plaque levels in cerebrospinal fluid, successfully diagnosed 15 Alzheimer's patients and wasn't tripped up by 19 people with other neurological diseases.

If the plaques prove a crucial link in Alzheimer's, a treatment that breaks them down may undo the damage. Claudio Soto and colleagues at New York University Medical Center may have found a protein fragment that does just that. In rats and tissue cultures of human nerve cells, these "beta sheet breakers" not only prevent amyloid plaques from forming, but also dissolve existing plaques.

Taken together, the new studies create exciting new tools for tackling Alzheimer's disease, says Robert Kisilevsky, a pathologist at Queens University in Kingston, Ontario. Early diagnosis could help doctors step in and use a new therapy to preserve brain cells, he says. And if beta sheet breakers prove effective in monkeys as well as rats, they might also help treat Alzheimer's patients. But that's not likely to be straight forward. To treat humans, researchers must still find a way to deliver the protein fragments past the blood-brain barrier, which prevents circulating proteins from entering the brain, and to the site of the plaques. Adds Kisilevsky, "these are formidable problems."

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