Scientists closer to early Alzheimer’s diagnosis

A painless skin test for Alzheimer’s disease? It may seem unlikely, but scientists at the Blanchette Rockefeller Neurosciences Institute (BRNI) have isolated a substance in skin cells that may provide doctors with a quick and accurate yes-or-no answer when they suspect a patient is showing early signs of the disease. The test could be performed easily by a nurse or medical technician in a doctor’s office or outpatient clinic.

In an article to be published online the week of Aug. 14 in the Proceedings of the National Academy of Sciences (PNAS), researchers at BRNI describe a biomarker that can accurately distinguish between Alzheimer’s disease and other forms of dementia during the first one to two years of the disease’s progression.
The BRNI biomarker showed high accuracy when tested with human skin cells from a tissue bank, as well as for samples obtained in a previous, unpublished study of patients with autopsy-confirmed diagnoses. The biomarker could also potentially be used with blood samples.

“When it begins, Alzheimer's disease is often difficult to distinguish from other dementias or mild cognitive impairment,” says Daniel L. Alkon, M.D., scientific director of BRNI and coauthor of the study with Tapan K. Khan, Ph.D., assistant professor. “Potential treatments of Alzheimer’s, however, are likely to have their greatest efficacy before the devastating and widespread impairment of brain function that inevitably develops after four or more years.”

Many scientists have concluded in recent years that Alzheimer’s effects are found throughout the body, not just in the brain. By testing for signs of Alzheimer’s-related inflammation in skin cells called fibroblasts, the BRNI team has located a biomarker for the disease that can be tested without the invasive tests previously required, such as a lumbar tap.

Alzheimer’s disease stimulates a change in the enzyme, MAP Kinase Erk 1/2. When fibroblasts are tested by exposing them to Bradykinin, a common inflammatory signal, the Erk 1/2 response in skin cells of Alzheimer’s patients was sharply distinguished from the results in cells from age-matched controls. It was also differentiated from the skin cells from patients with non-Alzheimer’s dementias, such as Parkinson's disease, multiple infarct dementia and Huntington's chorea.

Drs. Khan and Alkon have created an Alzheimer’s Index that may contribute greatly to physicians’ evaluations of patients with dementia. The index is a mathematical formula that allows the scientists to convert the test results for each patient to a single number.

“The results demonstrate that when the Alzheimer’s Index agrees with the clinical diagnosis of the presence of Alzheimer’s, there is a high probability of accurate diagnosis,” Alkon said.

The molecular pathway measured by the BRNI biomarker includes the same enzyme, PKC, which is targeted by the drug Bryostatin. BRNI is currently seeking approval to begin clinical trials of Bryostatin to determine if it is useful in treating both the symptoms and neurodegeneration of Alzheimer’s disease.

The article, “An Internally Controlled Peripheral Biomarker for Alzheimer’s Disease: Erk1 and Erk2 Responses to the Inflammatory Signal Bradykinin,” appears on the PNAS website, http://www.pnas.org/cgi/doi/10.1073/pnas.0605411103.

BRNI is an independent research center, affiliated with West Virginia University, which seeks to accelerate the transfer of basic neuroscience discoveries into practical treatments for patients suffering from Alzheimer's disease and other memory disorders.

U.S. Senator Jay Rockefeller founded the institute in memory of his mother, who died of Alzheimer's disease. For more information, see http://www.brni.org.