Early Warning? Spinal fluid may signal Alzheimer’s presence

Although it’s the most common type of dementia, Alzheimer’s disease is notoriously difficult to diagnose. When confronted with a confused and forgetful patient, a doctor must first rule out other brain disorders by putting the patient through a battery of psychological tests, brain scans, and various health assessments. The diagnosis can take months.

In search of a more precise diagnostic tool, researchers have been looking for signs of the disease in people’s spinal fluid.

In the September Archives of Neurology, a Swiss team reports that spinal-fluid concentrations of forms of two compounds already linked to the disease–tau protein and beta-amyloid peptide–may reveal whether a person has Alzheimer’s disease.

The researchers obtained spinal fluid from 51 people whom doctors had judged to have Alzheimer’s disease, 30 people with other forms of dementia, 19 people who had brain disorders not associated with dementia, and 31 healthy individuals. The average age of the participants was 67 years.

The Alzheimer’s patients had significantly less beta-amyloid peptide and more tau protein in their spinal fluid than people in the other three groups did, says study coauthor Christoph Hock of the University of Zurich. Both findings are consistent with results from previous studies by others.

Hock and his team took an additional step by calculating the ratio of tau protein to beta-amyloid peptide and found that Alzheimer’s patients averaged 147 times as much of the protein as the peptide, whereas healthy people averaged only 39 times as much. That ratio was calculated to be 74 for people with non-Alzheimer’s dementias and 48 for those with other brain disorders.

Knowing the ratio of tau to beta-amyloid could “help in early and accurate detection of Alzheimer’s disease,” Hock says.

Before the measurement can serve in the clinic, however, additional studies will be required, he says.

Alzheimer’s disease is marked by the death of brain cells, or neurons. Filaments of tau protein accumulate inside these cells, and plaques of beta-amyloid peptide collect outside the cells.

When neurons die, one hypothesis holds, they release tau into the spinal fluid, whereas beta-amyloid, being sticky, stays in the brain. In this study, the scientists measured phosphorylated tau, the major component of tau filaments, and beta-amyloid peptide42, the chief constituent of beta-amyloid.

There is no cure for Alzheimer’s disease, although drugs called acetylcholinesterase inhibitors improve symptoms in some people with mild disease. Researchers are investigating experimental drugs aimed at forestalling the brain damage, says Trey Sunderland of the National Institute of Mental Health in Bethesda, Md.

He and his colleagues are examining spinal fluid and blood samples from hundreds of people with a family history of Alzheimer’s disease to see whether tau and beta-amyloid measurements will reveal who is developing the disease, perhaps even before signs of the disease are apparent. If Alzheimer’s-preventing drugs are ever developed, spinal fluid tests to detect cases early would be especially valuable, he says.


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