Will I be next?

I AM CURLED up on my side, knees to my chest, hospital gown gaping in the back, when Liana Apostolova, MD, pulls out a needle that looks big enough to use on a baby elephant and takes aim at the space between a pair of vertebrae in my lower back. I am neither ill nor injured. I don’t have to be here. I am here for the sake of science—and because Apostolova is good at asking people to do this. Yet when she plunges the needle into my back, and the pressure begins to build to levels that can be only described as breathtaking, my commitment to science wavers. I forget why I am here.

Apostolova, a neurology professor at Indiana University School of Medicine and an internationally-respected authority on Alzheimer’s disease, is trying to answer some important questions about a little-studied subset of patients who happen to be at my same place in life. It is why I am allowing her to draw cerebrospinal fluid from my back like sap from a maple tree.

Alzheimer’s disease—that dreaded author of the long, slow goodbye—robs people of their memories, their personalities, their ability to care for themselves and, ultimately, life. It typically affects people older than 65. Yet for reasons unclear to science, Alzheimer’s also strikes a smaller portion of the population younger than that. Some in their 40s. Often, these are people who still have kids at home or in college. People who are still breadwinners for families. People just like me. And that—more than altruism or the quest for a story—is why I agreed to be Apostolova’s pin cushion, why I allowed her to test me with mind-bending memory questions, draw my blood, inject me with radioisotopes and take pictures of my brain with just about every conceivable technology known to medical science. All because I want a cure for a disease that strikes awfully close to home. And Liana Apostolova is a great candidate to find it.

BORN IN BULGARIA to a neuroscientist and a chemist, Apostolova really had no choice but to be a scientist. She grew up in labs while her parents worked. She went to the top high school in Bulgaria, a German-language prep school, and fell in love with, of all things, chemistry. She wanted to be a biochemist but her mother, a biochemist herself, suggested she first get her MD—because it was a noble profession and a steadier income—and then devote her life to science. When her mother was invited to work at Northwestern University, Liana stayed behind in Bulgaria for medical school. Soon, she realized she loved being around patients. And when she was exposed to neurology, she found another passion—the human brain.

“I never thought there was another specialty more interesting than this because cognition is what’s most unique to humans—the highest level of brain function,” she said.

Apostolova graduated summa cum laude from Medical University in Sofia, did a residency at the University of Iowa and a dementia fellowship at UCLA. There she made a name for herself by turning her sights on the genetic underpinnings of Alzheimer’s. And in 2015, IU—which had become a powerhouse in Alzheimer’s research—recruited her away from UCLA with some major philanthropic support. She was awarded the Barbara and Peer Baekgaard Chair in Alzheimer’s Disease Research, which Vera Bradley co-founder Barbara Baekgaard established in honor of her late husband. The Lilly Endowment’s Indiana Physician Scientist Initiative, which aims to recruit top talent, paid for Apostolova’s startup package.
We always thought we would resolve Alzheimer’s disease by studying the common late-onset form of the disease. Turns out, decades into that sort of research, we are still shy of understanding the disease biology in such detail to have a cure. So more study is necessary. Early-onset Alzheimer’s is one of the gaps that was missing.

We always thought we would resolve Alzheimer’s disease by studying the common late-onset form of the disease. Turns out, decades into that sort of research, we are still shy of understanding the disease biology in such detail to have a cure. So more study is necessary. Early-onset Alzheimer’s is one of the gaps that was missing.

The investment is starting to pay big dividends. Within two years of her arrival, Apostolova won a $7.6 million National Institutes of Health grant to lay the groundwork for the early-onset Alzheimer’s study. In October, the NIH followed that up with the largest single grant in IU history—$44.7 million to fund the study for another five years. It will be the largest ever done on early-onset Alzheimer’s disease.

In partnership with scientists from the Alzheimer’s Association, Harvard Medical School and the University of California, San Francisco, Apostolova will be directing an investigation that will involve 20 institutions around the country. She will be seeking answers to some key questions.

Why do some people develop Alzheimer’s so young?

Why is the disease so aggressive in younger patients?

What can be done to slow it?

Can it be stopped?

“We always thought we would resolve Alzheimer’s disease by studying the common late-onset form of the disease,” said Apostolova, surveying the science to date. “Turns out, decades into that sort of research, we are still shy of understanding the disease biology in such detail to have a cure. So more study is necessary. Early-onset Alzheimer’s is one of the gaps that was missing.”

Alzheimer’s disease currently affects an estimated 5.7 million Americans. As the population ages that number is expected to grow. Only about 200,000 cases involve people under 65, which is why this corner of the disease population has received less examination. Apostolova suspects there could be valuable data to be gleaned from younger patients that can help everyone with the disease. Older patients often face an assortment of health problems that contribute to dementia—from longstanding high blood pressure or type II diabetes to the basic wear and tear on the brain. With younger patients, most of those aging-related problems aren’t in the mix. As Apostolova puts it, “There is less noise in the data.”

To further reduce the noise, Apostolova’s study—the Longitudinal Early-onset Alzheimer’s Disease Study, or LEADS—will observe 400 patients who have been diagnosed with early-onset Alzheimer’s disease and 100 control subjects who have not. I am among the control subjects. Among those in the other category is Mary Estrada.

Mary Estrada’s early-onset Alzheimer’s disease went undiagnosed for two years, but her memory issues started in her late fifties.

THERE ARE FEW outward indications Estrada has Alzheimer’s. She drives around town without getting lost. She remembers her phone number. When you sit down and talk with her, there are no gaps in the conversation. She’s pleasant. She’s optimistic. But Estrada, now 63, has been experiencing a growing collection of memory problems since she was in her late 50s.

Many people misplace their mobile phones and they turn up in the couch, a coat pocket or an odd shelf. Estrada loses phones permanently—so many that she’s resorted to buying cheap burner phones. She’s lost a couple of wallets. She kept forgetting to eat lunch and lost 25 pounds. After dropping the weight she began fiddling with her loose wedding ring—and lost that, too. She’s done that twice.

“I get so tired of looking for what I just had in my hands—that I just put down” she said. In her characteristically upbeat attitude, Estrada looks at the bright side. “I get my steps in, easily,” she said, “just by walking through the house looking for things.”

Like so many early-onset patients, Estrada went undiagnosed for at least two years. One doctor chalked up her memory loss to her getting older. She said her concerns were just paranoia. But Estrada and her partner, Peggy Mack, knew better. So Estrada, who worked for the Indiana Department of Natural Resources, went to a clinic at the state government center. She took a memory test. And failed badly. It wasn’t even close.

At this point, I know my destiny is already there. I’m just going to go with the flow and accept it. Hopefully, this kind of study will make it easier for us.

Soon, someone pointed Estrada to Liana Apostolova. She put Estrada in the gown, put her on her side and tapped her spine as she did with me. After the testing, it was clear Estrada had an above average presence of the beta-amyloid protein—a hallmark of Alzheimer’s disease.

Estrada wasn’t surprised. She had watched her mother’s memory fade at a young age. Everyone always told her how much she looked and acted like her mother. So she suspected what Apostolova would say. To a degree, it even came as a relief. “I feel better that I know,” she said. “I think if I didn’t know what I was up against I’d be real worried.”

Without hesitation, Estrada agreed to participate in Apostolova’s study. Yes, she’d like to be the first person cured of Alzheimer’s. But she has no illusions. “At this point, I know my destiny is already there. I’m just going to go with the flow and accept it. Hopefully, this kind of study will make it easier for us. Hopefully, it won’t be as difficult as what my mother went through. That was many years ago.

AS OF YET, there’s no cure for Alzheimer’s and no treatment to slow its progress. It’s not even clear what exactly causes it.

What’s known is that a healthy brain is comprised of about 100 billion neurons, the cells that transmit nerve impulses across synapses to other neurons—bursts of information. As Alzheimer’s tightens its grip, these processes get disrupted.

Fragments of beta-amyloid begin to accumulate around neurons in the brain as early as two decades before a patient shows symptoms. “Just as with any other disease,” Apostolova said, “it takes a certain amount of damage before symptoms appear.” Much of the research, so far, has focused on removing amyloid. But it’s not clear whether this is the answer. Apostolova calls amyloid an “inciting factor” but perhaps not the sole component of the disease. “There are other downstream effects that also need to take place before damage starts occurring,” she said.

When another troublesome protein, tau, appears as tangles in the neurons, patients begin exhibiting symptoms, such as memory loss. Apostolova says there is an interplay between the two proteins that determines how quickly a patient declines.

To learn more about how the disease presents itself—and the rate of its advance—Apostolova constructed a study which splices the mind in just about every way possible short of cracking open the skull and taking a peek.

Hours of memory tests require subjects to recall lists of 10 to 15 words; remember numbers in a specific order, then remember them backward; look at a series of shapes and then draw them from memory; hear a story read to them and then recite it in as much detail as possible. Such tests left me feeling as if my brain was being parsed from the inside out. After a couple of hours, I needed a rest. I wanted a beer.

At another session, Apostolova gave me a physical exam, tested my reflexes, coordination and, again, my memory. She quizzed me on recent trips I’d taken, where I took my wife to eat last, what I ordered, what she ordered, where we sat. She checked my responses against my wife’s answers, obtained in a previous phone call.

Along the way, there were EKGs and blood draws and advanced imaging—an MRI and two PET scans—that required absolute stillness. To my surprise, this was more difficult to achieve than I’d expected. For the MRI, there are times I wasn’t allowed to blink, or to let my eyes twitch. The PET scans, which detect the presence of the worrisome proteins, weren’t quite as exacting but came with an added twist—the injection of a radioisotope, fluorine 18. The radiation level was low and, with a half-life of two hours, it fades quickly. But the technicians who work around the stuff every day try to limit their exposure. And while I was “hot,” in their parlance, they kept their distance.

The results were 2D pictures of my brain in black and white, and 3D pictures of my brain defined by an array of colored dots. Patients experiencing symptoms, such as memory loss, get some indications of what the pictures mean. Those of us without symptoms do not. Frankly, until Apostolova and her colleagues have some therapies, I’m OK with that.

All told, over the course of a month, these and other tests took more than 10 hours. Participants get some cash compensation, but their commitment must go beyond gas money. For control subjects like me, it’s usually a personal connection—to a patient or a researcher. For people like Estrada, it’s the hope for a cure. And Apostolova doesn’t think a cure is such a far-fetched idea. It’s possible, she said, there could be some therapies within a few years to slow the progression of the disease. After that, there could be a drug to stop it. Maybe even soon enough to help Mary Estrada.

“We’re not going to give up hope for any of our patients,” Apostolova said. “Definitely.”