Alzheimer's disease damages the minds of one in two people by age 85. Because this illness can progress insidiously for decades, as many as one in four people may already have Alzheimer’s at age 65, but not know it. Despite the number of people Alzheimer’s affects, its diagnosis is problematic. Recent discoveries by Stanford neurology instructor Markus Britschgi and his collaborators, however, may allow doctors to accurately diagnose Alzheimer’s years before symptoms appear.

Diagnosing Alzheimer’s disease is a tedious process of eliminating other plausible ailments. Patients often live with impairments for years before diagnosis, and some cases remain inconclusive while the patient is alive. Many scientists have turned their attention to making earlier diagnoses possible, sparing patients and their loved ones from agonizing over uncertainty.

Britschgi is one such scientist. As a postdoc in Stanford associate professor of neurology Tony Wyss-Coray’s lab, Britschgi had the chance to tackle neuroscience challenges at an exciting juncture in the field. Until a few years ago, people thought the brain was excluded from the body’s immune system. Then came the discovery that the immune system can affect the brain—in good and bad ways—through molecule exchange, and that brain degeneration leaves peripheral clues in the form of molecules that circulate in the bloodstream.

Britschgi got involved investigating Alzheimer’s biomarkers in blood while working with Wyss-Coray and Sandip Ray of Satoris Inc., a Bay Area company co-founded by Wyss-Coray with the goal of developing a blood test for the early detection of Alzheimer’s disease. Britschgi and Ray obtained 259 blood plasma samples from subjects who showed symptoms of various Alzheimer’s stages, as well as from controls. They used some of the samples to identify protein expression patterns in blood, contrasting samples from Alzheimer patients to samples from controls.

Wyss-Coray and Britschgi compare the communication between cells to language, with cells using bloodstream-traveling individual protein molecules as ‘words.’ “These ‘words’ tell other cells what to do, and so the cells can communicate over very long distances in the body,” Britschgi says.

Cells can release these ‘words’ into the bloodstream at varying amounts, and the ‘chatter’ in the blood thus takes on different qualities. That chatter is distinct between the blood of Alzheimer’s patients and non-afflicted people.

Of the 120 proteins Britschgi and Ray examined, 18 were enough to make up a pattern indicating Alzheimer’s. The Alzheimer’s patterns these 18 proteins displayed matched clinical Alzheimer’s diagnoses 90 percent of the time, and non-Alzheimer’s patterns matched subjects without the disease 88 percent of the time.

Next, the team tested if their biomarkers could predict future Alzheimer’s development. Using blood samples drawn from subjects diagnosed with only mild cognitive impairment two to six years prior, they found their method indeed could predict subsequent Alzheimer’s cases, in 91 percent of clinically diagnosed patients. Britschgi and Ray’s findings were published in the November 2007 issue of Nature Medicine.

While early Alzheimer’s diagnosis already benefits those who wish to take the disease into account when making life plans, it will truly be valuable when effective Alzheimer’s treatments are available. Britschgi and his colleagues are working on that too.

“With this tool, we’re not only diagnosing, but we can see the pattern of molecules that change,” Britschgi says. “These could indicate biological pathways that may be dysfunctional.”

Britschgi is excited about using mouse models to further research into these molecule patterns, with the goal of creating treatments from his discoveries. While plans for Alzheimer’s testing kits for physicians are in the pipelines elsewhere, “our lab here is interested in the biological functions of these molecules, and how we can manipulate them for a beneficial outcome,” Britschgi says.

For more information on this research, visit: http://med.stanford.edu/profiles/Markus_Britschgi/
http://dsresearch.stanford.edu/about/wyss_coray.html