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What Our Biomarkers Can Tell Us

The discovery of internal indicators of Parkinson's, Alzheimer's and other conditions could help delay symptoms and speed treatment

You know that your cholesterol level and blood pressure measurements can help predict your chances of having a heart attack or stroke. But what if doctors could predict whether you're destined to develop Alzheimer's disease, Parkinson's disease or even how healthfully you'll age?
In labs and universities worldwide, scientists are studying and searching for biomarkers — measurable molecules in human blood, fluids or tissues that can indicate the presence or likelihood of a condition. The hope is that more such markers can be identified and proven reliable for predicting neurological illness or frailty in people while they still appear healthy.

Biomarkers could also be useful in evaluating the effectiveness of treatments designed to slow or halt the progression of disease. Past medications created to limit brain damage from Alzheimer's, for example, may not have succeeded because they were tested in people who already had symptoms, when it was too late to have an impact.

(MORE: Why Predictive Health Should Be the Future of Medicine)

"There's growing research that the underlying biology in Alzheimer's disease is actually occurring a decade or more before symptoms appear," says Heather Snyder, director of medical and scientific operations at the Alzheimer's Association in Chicago.
Hope for Alzheimer's Treatment

Some seemingly promising biomarkers for Alzheimer's and Parkinson's are now the focus of international studies. These proteins, including beta amyloid and tau, are found in cerebrospinal fluid in the brain and spinal cord.

The discovery of such biomarkers moves science beyond genetic testing. Today, such testing provides clues about a person's risk of developing Alzheimer's, but it can't reveal whether symptoms have already stealthily begun to emerge. For example, one variation of a gene called apolipoprotein E (APOE) is associated with a higher risk of the disease after age 65, but not everyone with the variation develops Alzheimer's, and many people who don't have the variation do.
(MORE: Early Alzheimer's Detection: Is It Worth Knowing?)

A new trial to advance our ability to detect nascent signs of Alzheimer's, and hopefully treat them, is about to launch. The "Anti-Amyloid Treatment in Asymptomatic AD" trial, also known as the A4 Trial, is funded by the National Institutes of Health's National Institute on Aging.

Researchers will screen about 1,000 apparently asymptomatic volunteers 65 and older across the country using PET (positron emission tomography) scans to seek evidence of beta amyloid plaque accumulation in the brain, widely recognized as a hallmark of the condition.

Participants will randomly be given either a placebo or an experimental anti-amyloid drug that has proven ineffective in patients with severe Alzheimer's but modestly beneficial for people with mild symptoms. The goal is to see whether fewer people in the anti-amyloid drug group go on to develop Alzheimer's symptoms.

Spotting Signs of Parkinson's

While beta-amyloid and tau protein levels are elevated in Alzheimer's patients, they're reduced in the brains of those with Parkinson's disease, according to a report released this summer by the Parkinson's Progression Marker Initiative (PPMI), a collaborative effort of drug manufacturers and academic research centers in the U.S., Europe and Australia sponsored by the Michael J. Fox Foundation.

PPMI researchers compared levels of beta-amyloid and tau in 39 people without Parkinson's and 63 patients at the earliest stage of the disease, who had not yet begun a medication regimen. The team found lower levels of the proteins in the Parkinson's patients, and those with the lowest levels were more likely to have trouble with walking and balance, a combination associated with more rapid progression of the condition.

PPMI scientists plan a larger follow-up study and research into biomarker levels in adults with early signs of Parkinson's, such as a compromised sense of smell and a specific type of sleep disorder, as well as those who have one of two genetic mutations often linked to Parkinson's.

If further research confirms the usefulness of these biomarkers, scientists can begin testing the effect of different treatments on presymptomatic patients with the hope of staving off effects of the disease, says Leslie Shaw, one of the directors of the project and a professor in the department of pathology and lab medicine at the University of Pennsylvania.

Research has also explored the usefulness as a biomarker of a third protein, alpha-sinuclein, which helps make up the protein clumps known as Lewy bodies, a typical sign of Parkinson's progression. A study released this fall by researchers from Boston's Beth Israel Deaconess Medical Center found levels of the protein to be elevated in the skin of Parkinson's patients, even at the earliest stages of the disease.

Does Aging Have Markers?

Scientists seeking ways to limit the effects of aging on the body have been working to identify biomarkers of healthy aging but so far it has been a struggle. "Whether you could identify some individual people who are aging more slowly than average is not really clear," says Richard Miller, associate director for research at the University of Michigan Geriatrics Center.

Relevant biomarkers of aging would not be related to visual signs like wrinkles, which are more a factor of sun exposure than the passage of time. Instead, researchers search for indications that typically decline with age, such as the level of antibodies produced by the immune system in response to a flu shot, or the ability to hear high-pitched sounds.

Identifying biomarkers related to these would be useful in evaluating adults' true "biological age, certainly better than commercial online questionnaires, which are at best unreliable and at worst scams. Once biomarkers of aging can be determined, researchers can better determine whether practices such as calorie restriction can truly slow the aging process, Miller says. As of now, though, the only way to test such theories is to track subjects' health for decades.
(MORE: The Ruthless, Fruitless Pursuit of Immortality)

As for signs of unhealthy aging, Miller says, we already know of plenty: "Most people in their 50s and 60s know whether they're grossly overweight, partly overweight or at a healthy weight range," he says. "They know whether they have hypertension or not. They know whether they smoke or not."

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