November 26, 2007
Scientists at Stanford University have identified a handful of abnormal proteins in the blood that may signal the onset of Alzheimer's disease at its earliest stages, two to six years before debilitating memory loss and other serious symptoms arise. While much more testing is needed to confirm the findings, they could one day lead to a simple blood test to diagnose Alzheimer's at its earliest stages, when medications and other yet to be developed treatments, may be most effective. The findings were reported in the medical journal Nature Medicine.
The test identifies changes in a handful of proteins in the blood that cells use to convey messages to one another. The blood test identified who had Alzheimer's with 90 percent agreement with clinical diagnoses. In about 80 percent of cases, it could also predict if people with mild cognitive impairment, a less serious form of memory loss, would develop Alzheimer's several years later. "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 Stanford neurologist Tony Wyss-Coray, Ph.D., the senior author of the study. "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."
Currently, doctors typically diagnose Alzheimer's when memory loss, confusion, and other symptoms become prominent and other causes, such as strokes, tumors, or medication side effects, have been ruled out. At that point, the disease has already done irreparable damage to the brain. Doctors have a good idea that Alzheimer's is present about 90 percent of the time. Still, the only definitive diagnosis is by brain autopsy after a person has died. Scientists are studying a range of technologies that image the brain, including PET, MRI, CT, and SPECT scans that may distinguish "senior moments" from more worrisome memory lapses. They are also conducting research into markers in the blood, spinal fluid, urine, skin, or other tissues that may signal an early diagnosis of Alzheimer's. The hope is that early diagnosis may lead to new treatments that halt, or even reverse, the relentless downward progression of disease.
A Trail of Clues
The idea for the current blood test began when researchers measured levels of 120 different proteins in the blood that are used by cells to communicate with one another. By comparing blood samples from five people diagnosed with Alzheimer's with those from five mentally intact peers, they found striking differences between the two groups. "This study made me realize that we should get away from this image of a brain isolated from the body," said Markus Britschgi, Ph.D., who was involved in the ongoing research. "The brain is part of the body and so it's connected in one huge network."
The research was expanded to 259 blood samples collected from clinics in the United States, Sweden, Poland and Italy. Some were from people with Alzheimer's. Others were from those with mild cognitive impairment or from mentally alert individuals. The investigators identified 18 proteins in the blood that correlated closely with Alzheimer's disease. They then tested the 18 proteins in an additional 92 blood samples. The protein analysis matched the clinical diagnosis 90 percent of the time. The researchers then asked if they could predict the development of Alzheimer's among 47 people with mild cognitive impairment who had been part of the study for two to six years. The test, done on blood samples taken several years earlier, flagged more than 80 percent of the patients who developed Alzheimer's two to six years later.
The researchers speculate that the blood markers they identified may involve cells that clear beta-amyloid, a toxic protein that builds up in the brains of those with Alzheimer's. The immune system may also be involved. Animal experiments indicate that the brain in Alzheimer's may send out signals to the body's immune system, and some of the cells involved in the current marker experiment are important in immune system function. The findings must now be confirmed in other labs and in much larger studies, a process that could take years. Other kinds of markers have been identified in the past but were not validated in further testing.
By www.ALZinfo.org, The Alzheimer's Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer's Research Foundation at The Rockefeller University.
Nature Medicine, online edition, October 15, 2007. Stanford University School of Medicine Press Office.