Early testing for Alzheimer’s

Spinal fluid compounds can predict in many cases whether people with mild cognitive impairments will develop the disease

Elderly people with mild cognitive losses are at a heightened risk of progressing to Alzheimer’s disease if they have a combination of telltale compounds in their spinal fluid, researchers report in the July 22/29 Journal of the American Medical Association.

By testing for a shortage of a sticky compound called amyloid-beta in the spinal fluid and for excess amounts of two kinds of a protein called tau, the scientists could identify people at greatest risk.

The test isn’t foolproof, and a positive reading still warns of a disease for which there is no cure. But scientists are heartened by this and earlier studies (SN: 9/20/03, p. 179)because Alzheimer’s disease is difficult to foresee and its early symptoms are often mistaken for routine cognitive losses caused by aging.

Niklas Mattsson of a Gothenburg University-affiliated hospital in Mölndal, Sweden, and an international group of scientists recruited 750 elderly people in Europe and the United States from 1990 to 2007. At the time of enrollment, the volunteers had mild cognitive impairment — a loss of memory or other mental faculties — that wasn’t attributable to aging alone but fell short of Alzheimer’s disease. Each volunteer contributed a cerebrospinal fluid sample by undergoing a spinal puncture. The participants, average age 69, were monitored for about three years during the study.

Those who developed Alzheimer’s disease were more likely to have had less amyloid-beta or more tau in their spinal fluid than those who didn’t develop Alzheimer’s. People who had both low amyloid-beta and high tau levels were five times as likely to develop Alzheimer’s disease during the study as were those with normal spinal fluid profiles, Mattsson says.

The screening test correctly predicted incipient Alzheimer’s disease 83 percent of the time. Studies that track elderly patients longer may show an increased accuracy rate because patients whose spinal fluid tested positive may develop Alzheimer’s disease later, says Ronald Petersen, a neurologist at the Mayo Clinic in Rochester, Minn.

Since spinal fluid bathes the entire central nervous system, its components can serve as markers for what’s going on in the brain. Although the precise biological course of Alzheimer’s is murky, many scientists theorize that amyloid-beta accumulates in the brain early in the disease process, leaving less to circulate in the spinal fluid, Petersen says. Later, tau is released from dying brain cells into the spinal fluid, increasing tau levels there.

Roughly half of all elderly people with mild cognitive impairments later develop Alzheimer’s disease, says Mattsson, a physician and neuroscientist. Currently available drugs treat only Alzheimer’s symptoms, not the disease.

By fine-tuning this screening test, Mattsson, Petersen and others are planning for the day when other research teams develop drugs to arrest or reverse the brain damage that marks the disease. There are up to 100 such experimental Alzheimer’s drugs currently in development, Petersen says. “Almost every major pharmaceutical house has a program for Alzheimer’s.”

If such medications become available, accurate diagnosis will become paramount in determining how to prescribe them, Mattsson says. “It’s very important to interfere with the disease as early as possible, and this is where the diagnostic test comes in.” Screening for changes in amyloid-beta and tau in drug trial participants might also indicate which medications are thwarting the disease process, Mattsson says.

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