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previous, unpublished study of patients with autopsy-confirmed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.