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Researchers seeking ‘biomarkers’ that could help prevent Alzheimer’s

Tue., July 1, 2014, midnight

Dean Hartley speaks to community members about Alzheimer’s research last Tuesday at Gonzaga Law School’s Barbieri Courtroom in Spokane. (Tyler Tjomsland)
Dean Hartley speaks to community members about Alzheimer’s research last Tuesday at Gonzaga Law School’s Barbieri Courtroom in Spokane. (Tyler Tjomsland)

Diagnosis day is life-changing for Alzheimer’s disease patients and their families.

But Alzheimer’s actually begins years before it’s progressed far enough to produce the symptoms – memory problems, disorientation, trouble speaking and writing – that lead to a diagnosis.

The disease’s “silent phase” can last 20 years, Dean Hartley, science director for the national Alzheimer’s Association, told a Spokane audience last week.

That’s why researchers, along with seeking effective treatments for the fatal disease, are working to identify “biomarkers” of Alzheimer’s that signal the disease is already underway or a patient is at risk of developing it, allowing treatment to be delivered earlier.

Alzheimer’s is the most common type of dementia, affecting about 1 in 9 people in the U.S. age 65 and older. Patients eventually become unable to perform basic functions such as walking and swallowing.

In town to provide an update on Alzheimer’s research at a public presentation at Gonzaga University, Hartley said scientists are searching for drugs to treat the disease, but also for its early signs hidden in the body.

Like high cholesterol signals a high risk of cardiovascular disease, a biological marker is some measurable substance in the body that indicates illness. By identifying the biomarkers associated with Alzheimer’s before it degrades patients’ brains, researchers hope to eventually be able to identify it before patients suffer the losses typical of the disease.

The risk of Alzheimer’s rises significantly at 65, but scientists believe the disease really starts as long as 20 years before its symptoms show up, Hartley said. So a biomarker – identified through standard testing – could indicate either a risk of developing Alzheimer’s or that the disease has already begun around age 45, Hartley said.

“That would be the first stage, to say, ‘Oh, you’re at risk. Now what we want to do is plug in the therapy before you develop the signs,’ ” Hartley said. “Because once the signs show up, that means something’s already structurally wrong with the brain.”

Researchers are looking for Alzheimer’s biomarkers in our genes, in our psychological processes and behaviors, in the clear fluid in our spinal columns that cushions our brains and spinal cords.

They’re also looking at the brains of living patients. While Alzheimer’s has in the past been diagnosable only after the patient’s death, through autopsy, “amyloid PET imaging” is among tools allowing doctors to see what’s going on in a living person’s brain, enabling at least probable diagnoses.

The formation of plaques in the brain is a hallmark of Alzheimer’s. The imaging technique lets doctors see these buildups, made of a protein called beta-amyloid.

“This, I think, is a game changer for us,” Hartley said.

Among several major prevention trials underway, a research partnership known as DIAN focuses on people who have a rare mutated “deterministic gene”; not only will the individuals develop the disease for sure, but they’ll develop it at the same age their parents did.

DIAN, or Dominantly Inherited Alzheimer Network, researchers have found that amyloid buildup in study participants’ brains started almost 20 years earlier than the normal clinical diagnosis of Alzheimer’s.

That’s information scientists didn’t have five years ago, Hartley said.

“That we’re able to look into the brain is extremely valuable in where we’re going with this disease,” he said. “It may suggest there is a much larger window for treating these individuals, a window of opportunity.”

While spinal taps and brain scans ultimately are too impractical and expensive for standard testing, Hartley said simpler Alzheimer’s-detecting blood tests are on the horizon.

The problem, of course, is that the therapies to effectively treat the disease also have yet to be developed, although clinical trials are underway.

Current Alzheimer’s drugs, such as Aricept and Namenda, treat the symptoms – possibly improving an Alzheimer’s patient’s memory for a period of time – but the disease continues to progress.

“At some point the drugs no longer work,” Hartley said.

Still, early diagnosis makes a difference, with the drugs providing maybe 18 months of improved memory, Hartley said: “Giving them anything back is better than nothing.”

Research – and research funding – are vital to the process, Hartley said.

It took three lumbar punctures to collect it, but Spokane resident Amy Shives, 56, gave a sample of her spinal fluid to researchers at the University of California, San Francisco.

Biomarker research has suggested that Alzheimer’s in its earliest stages causes changes in proteins found in cerebrospinal fluid, the clear fluid that cushions the brain and spinal cord. Shives makes an annual, weeklong trip to California to participate in multiple Alzheimer’s research projects, undergoing genetic tests, eye tests, brain scans and more tests.

Shives was diagnosed with Alzheimer’s at 53. Her mother, who was diagnosed at the same age, died of the disease.

Still, it took a lot of effort to convince skeptical doctors she might have the disease, Shives said, and her diagnosis followed many tests as doctors ruled out other explanations for her memory loss and fatigue.

Now she’s an advocate for Alzheimer’s patients, recently named an adviser to the national board of directors for the Alzheimer’s Association. And Shives, a former counselor at Spokane Community College, said she’s committed to participating in the research studies until her death, after which her brain will be donated for more research.

“I guess the bottom line is that I have two daughters,” she said. “There isn’t anything for me as far as a cure or really any help for me on the horizon. But my daughters are in their 20s. So it’s important to me to do what I can for the future, for future generations.”

The Alzheimer’s Association connects potential participants with research studies through its TrialMatch database, which includes drug and non-drug studies conducted at sites across the U.S.

“We’re looking for everybody, and healthy people, too,” said Joel Loiacono, executive director of the Inland Northwest chapter of the Alzheimer’s Association.

Some drug studies also help further the search for useful biomarkers, and vice versa. And while there’s no “silver bullet” to treat Alzheimer’s now, Loiacono said, “when we do hit pay dirt, we do want to be able to identify the people who are at risk.”



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