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New Test May Predict Conversion From Mild Cognitive Impairment To Alzheimer's Disease

March 17, 2009

Adapted from the University of Pennsylvania School of Medicine

A test capable of confirming or ruling out Alzheimer's disease has been validated and standardized by researchers at the University of Pennsylvania School of Medicine. By measuring cerebrospinal fluid (CSF) concentrations of two of the disease's biochemical hallmarks—amyloid beta42 peptide and tau protein—the test also predicted whether a person's mild cognitive impairment would convert to Alzheimer's disease over time. Researchers were able to detect this devastating disease at the earliest stages, before dementia symptoms appeared and widespread irreversible damage occurred. The findings hold promise in the search for effective pharmaceutical therapies capable of halting the disease.

A team of Penn Medicine researchers, led by Leslie M. Shaw, Ph.D., Co-Director of the Penn Alzheimer's Disease Neuroimaging Initiative (ADNI) Biomarker Core, found evidence of neuron degeneration—marked by an increase in CSF concentration of tau proteins—and plaque deposition, indicated by a decrease in amyloid beta42 concentration. In addition, people with two copies of the genetic risk factor for Alzheimer's disease, ApoE4 , had the lowest concentrations of amyloid beta42, compared to those with one or no copies. The study appears in the online edition of the Annals of Neurology.

"With this test, we can reliably detect and track the progression of Alzheimer's disease," said Dr. Shaw. "Validated biomarker tests will improve the focus of Alzheimer's clinical trials, enrolling patients at earlier stages of the disease to find treatments that can at least delay—and perhaps stop— neurodegeneration. In addition, prevention trials can test methods to delay or block mild cognitive impairment from converting to full-blown Alzheimer's."

Further validation studies of this research test system are underway. Additional work is needed to develop additional biomarkers, as well as identify more genetic risk factors that will help distinguish Alzheimer's from other neurodegenerative diseases characterized by cognitive impairments.

"Thanks to the dedicated researchers and volunteers who participated in this and other Alzheimer's disease studies through the Penn Alzheimer's Disease Core Center and at ADNI trial sites around the US and Canada, we have validated a test where a safe, simple lumbar puncture can provide information to confirm suspected Alzheimer's disease and predict the onset of the disease," said John Q. Trojanowski, M.D., Ph.D., Director of the Penn Alzheimer's Disease Core Center. "Using this technique, we will further our understanding of how the disease progresses and what we can do to stop Alzheimer's disease before it starts."

Guy Eakin, Ph.D., Director of Research Grants at the BrightFocus Foundation, added, “There are currently no disease-modifying treatments for Alzheimer's disease; existing therapies treat only symptoms of the disease. It is widely believed that advances of new therapies will be facilitated by the ability to detect Alzheimer's disease at its earliest stages. Spinal fluid tests such as the one developed by Dr. Shaw are clinically feasible and provide both doctors and researchers with the much needed ability to detect Alzheimer's disease earlier in the disease progression than currently available tests.”

Beyond clinical diagnosis, these types of tests pave many new ways for researchers to address the basic factors that affect a person's risk for developing Alzheimer's disease. Dr. Alison Goate of Washington University, St. Louis, is receiving research funds from the BrightFocus Foundation to identify new genes involved in the development of late onset Alzheimer's disease, using similar spinal fluid screening tests.

“The spinal fluid tests provide some advantages over a classic study comparing [Alzheimer's disease] cases and [normal control groups]. These measurements are precise and can be measured in everyone regardless of age. They also provide a biological framework to understand the disease. When two people have different levels of the biomarker in their spinal fluid, some of the difference is probably due to genetic influences. We hope to use this variability to find new genes that affect the risk for developing Alzheimer's disease,” says Dr. Goate. The genes identified by Dr. Goate's work may help provide a basic understanding of the molecular causes of Alzheimer's disease and may be used in development of the next generation of drugs to treat Alzheimer's disease and for early diagnostic tests.

Alzheimer's disease is a devastating disease, affecting an estimated 26 million people globally. Experts predict this number will grow to 106 million by 2050.


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Some of the content in this section is adapted from other sources, which are clearly identified within each individual item of information.

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