Signaling Blood Proteins Predict and Indicate Alzheimer's Disease

A blood test identifies changes in a handful of proteins in blood plasma that cells use to convey messages to one another. These changes could foretell a connection between shifts in the cellular dialog and changes in the brain accompanying Alzheimer's disease.

One of the most distressing aspects of Alzheimer's disease is the difficulty in determining whether mild memory problems are the beginning of an inevitable mental decline. Currently, the clinical diagnosis for Alzheimer's is one of exclusion--by testing for other causes of memory loss and cognitive declines, such as stroke, tumors, and alcoholism. If those conditions are eliminated as causes of memory loss, what remains is Alzheimer's, which is the most common cause of dementia. Even the clinical diagnosis is imperfect, and the only definitive diagnosis is by brain autopsy after a person has died.

Investigators collected a total of 259 blood samples from individuals with presymptomatic to late-stage Alzheimer's disease, and from those without the disease. Using so-called "signal profiling,” researchers were able to simultaneously measure the relative abundance of 120 known proteins found in plasma that function as chemical messengers between blood cells, brain cells, and cells of the immune system.

Statistical analyses of the two groups of blood samples showed there were 18 proteins in the Alzheimer's samples that expressed distinctly different concentrations from those in normal individuals. The different protein expression pattern found in the Alzheimer's samples was statistically significant, with nearly 90% accuracy in diagnosing and characterizing the disease.

A group of cell-signaling proteins found in blood serve as a unique "voiceprint” that can not only be used to diagnose Alzheimer's disease, but also to classify and predict presymptomatic individuals who will eventually develop the memory-robbing disorder.

"Our technology enables us to 'listen' to the chatter of cells communicating with each other and determine if there's anything abnormal,” said Tony Wyss-Coray, Ph.D., a lead scientist in the study, and a co-founder of San Francisco-based Satoris, Inc. (San Francisco, CA, USA; www.satoris.com). "Our data indicate blood contains a highly specific, biologic signature that can characterize Alzheimer's disease years before a clinical diagnosis can be made.”

Listening to cells' messages may not only lead to the first noninvasive diagnostic test for Alzheimer's, it could also lead to similar discoveries about other disorders by focusing on what cells use to talk to each other, according to Tony Wyss-Coray, Ph.D., who is also associate professor of neurology and neurological sciences at Stanford University (Stanford, CA, USA) and a member of the Geriatric Research, Education, and Clinical Center at the Veterans Affairs Palo Alto Health Care System (Palo Alto, CA, USA).

"Just as a psychiatrist can conclude a lot of things by listening to the words of a patient, so by ‘listening' to different proteins we are measuring whether something is going wrong in the cells, said Prof. Wyss-Coray. "It's not that the cells are using new words when something goes wrong. It's just that some words are much stronger and some are much weaker; the chatter has a different tone.”

The findings show that it is possible to use factors in the blood to diagnose and even predict the disease, but the authors emphasized, this must now be confirmed in other labs. The study appeared in the October 15, 2007, advance online edition of the journal Nature Medicine.


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