From Our 2009 Archives

Biomarkers May Predict Alzheimer's

By Steven Reinberg
HealthDay Reporter

TUESDAY, July 21 (HealthDay News) -- Certain proteins found in cerebrospinal fluid may accurately identify the people with mild cognitive impairment who are most likely to develop Alzheimer's disease, a new study finds.

Changes in the chemistry of cerebrospinal fluid have been identified as early signs of Alzheimer's disease. If and when treatments are available for Alzheimer's, diagnosing the disease early may help prevent it from developing, experts say.

"We confirmed, in a large multi-center study, that proteins in cerebrospinal fluid identify early-stage Alzheimer's disease, as suggested by previous smaller studies," said lead researcher Dr. Niklas Mattsson, from the Institute of Neuroscience and Physiology, Clinical Neurochemistry Laboratory at Sahlgrenska University Hospital in Molndal, Sweden.

"These proteins may be used in research, in particular in drug trials, and also as a complement to clinical diagnostics, in particular when disease-modifying drugs become available," he said.

The report is published in the July 22/29 issue of the Journal of the American Medical Association.

For the study, Mattsson's team studied the accuracy of using three biomarkers found in spinal fluid in predicting Alzheimer's diseases. The biomarkers are beta-amyloid1-42 (Aβ42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau).

The researchers tested for these biomarkers in 750 people with mild cognitive impairment, 529 people with Alzheimer's disease and 304 healthy people. After two years, 271 of those with mild cognitive impairment progressed to Alzheimer's disease and 59 developed other dementias.

The researchers found that people who developed Alzheimer's had lower levels of Aβ42 and higher levels of P-tau and T-tau compared with patients with mild cognitive impairment who did not develop Alzheimer's.

Mattsson's group found these biomarkers were highly accurate in predicting which patients would develop Alzheimer's disease. "The cerebrospinal fluid proteins Aβ42, T-tau, and P-tau are useful in diagnosis of early-stage Alzheimer's disease," Mattsson noted.

Dr. Sam Gandy, the Mount Sinai Professor in Alzheimer's Disease Research at Mount Sinai School of Medicine in New York City, said this study really quantifies the accuracy of these tests in predicting Alzheimer's.

"There have been a number of smaller reports that Aβ falls and P-tau rises as the clinical course progresses from aging to mild cognitive impairment to Alzheimer's," Gandy said. "The sensitivities and specificities of these smaller studies have varied widely."

This larger study is definitive in establishing sensitivity and specificity that are somewhat lower than those reported by the smaller studies, Gandy said. "The larger study also points up the importance of harmonizing assays across multiple study sites in order to optimize the sensitivity and specificity."

Maria Carrillo, director of medical and scientific relations at the Alzheimer's Association, hopes that one day Alzheimer's can be screened for as routinely as cholesterol levels are checked today.

"We are very excited that cerebrospinal fluid biomarkers are holding up in terms of their specificity and sensitivity in diagnosing the disease early," Carrillo said. "The next step is to make sure these tests are standardized so that the test will mean the same thing, no matter where it is taken."

If these tests are standardized, it could be a biomarker that identifies the disease, Carrillo said. "If over the next two or three years we also have a therapy, then we need to examine how that therapy works in an incipient form of Alzheimer's, not once those memories have already started fading," she said.

SOURCES: Niklas Mattsson, M.D., Institute of Neuroscience and Physiology, Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Molndal, Sweden; Maria Carrillo, Ph.D., director, medical and scientific relations, Alzheimer's Association; Samuel Gandy, M.D., Ph.D., Mount Sinai Professor in Alzheimer's Disease Research, Mount Sinai School of Medicine, New York City; July 22/29, 2009, Journal of the American Medical Association

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