Local Researchers Blaze New Trails in the Search for Causes of Alzheimer's Disease

Jun 12, 2017

More than five million Americans suffer from Alzheimer’s Disease.

And according to the Alzheimer’s Association, that number could double in the next two decades as baby boomers age and people live longer.

Despite massive research efforts, we still don’t know the root causes of the disease or how to treat it.

That’s why local researchers are looking in new directions to solve the mystery of Alzheimer’s, as WKSU’s Jeff St.Clair reports in this week’s Exploradio.

Christine Crish is a researcher at the Northeast Ohio Medical University in Rootstown.

She began her career studying a bizarre creature called the naked mole rat.

“It’s kind of a weird story,” she says.

Because the hairless rodents live in underground colonies, that, like bees, are led by a queen, and this queen does something very unusual…

“She actually physically grew bigger every time she had a pregnancy, and she was an adult animal this shouldn’t be happening. Her bones were expanding. Her lumbar spine was elongating.”

Crish went from studying bone growth in naked mole rats to learning how bones grow and shrink in adult humans, and this led to a little studied area of Alzheimer’s research.

Dr. Christine Crish is a researcher at NEOMED. Her recent work uncovers the connection between bone loss and Alzheimer's pathology.
Credit JEFF ST.CLAIR / WKSU

“We think we’re noticing that many of our early Alzheimer’s patients have osteoporosis, or reduced bone density,” says Crish

Crish says for some reason other researchers never followed up on this clue - “and that perplexed me. It still perplexes me.”

So now she’s working to figure how bone loss is related to Alzheimer’s.

Alzheimer's and the Brainstem 
Crish's interest in bone loss led her to study a part of the brain not normally associated with the disease, the brainstem.

“Something in that disease process is affecting the brainstem very early on before it reaches the forebrain where all of those learning and memory structures are,” says Crish.

She says the brainstem is important because that’s where most of the brain’s supply of serotonin is made.

We've been focusing on amyloid beta for 30 years and we don't have a clear explanation yet, so perhaps we might want to look at everything else.

Serotonin is known to influence a host of things from mood to digestion, but it also sets off a complicated cascade of signaling in the brain that helps keep bones strong.

And Crish says, when it’s disrupted by a disease like Alzheimer’s, we see changes in a number of basic functions like the regulation of bone mass, mood, appetite, and blood chemistry.

Crish thinks in Alzheimer's Disease the brainstem may be affected first, "and by the time we’re in learning and memory structures it’s just too late.”

Crish says the brainstem could even be the conduit for the spread of Alzheimer’s throughout the brain.

“These cells – these groups of cells – project to just about every place in the brain and they send serotonin everywhere up there.”

She thinks bone density loss should be added to the early warning signs of Alzheimer’s.

She even suggests boosting the amount of serotonin in the brain as a way of slowing its progress.

Alzheimer's and Hormones
Only around 10 percent of Alzheimer’s cases can be traced to aberrant genes, according to Jason Richardson, head of the Neurodegenerative Disease Focus Area at NEOMED.

Dr. Jason Richardson is director of the Neurodegenerative Disease & Aging Research Focus Area at NEOMED.
Credit JEFF ST.CLAIR / WKSU

He says in the other 90 percent of patients, “we don’t know what causes it.”

He says it’s important to try new ways to attack the problem of Alzheimer’s.

“We’re dealing with this huge public health issue. We’ve got an aging population, it’s going to swamp people in the next 30 years.  So people are thinking outside the box, and really taking some chances.”

One clue that Kent State researcher Gemma Casadesus is following is that women are twice as likely to get Alzheimer’s as men.

“One major difference between men and women," says Casadesus, is that at about the age of 50 women's production of estrogen stops, "and you’re done.”

She says this sudden drop-off of a crucial hormone is bad for a woman’s brain, "your neurons are like ouch…”

That’s because estrogen provides what’s called a neuroprotective effect -  sopping up free radicals and keeping nerve cells from wearing out.

But menopause delivers a one-two punch, according to Casadesus, because the steep drop in estrogen also leads to lower levels in the brain of a hormone that she believes helps stave off age-related declines.

Leaving Amyloid Beta Behind
In a newly discovered pathway, Casadesus has found that luteinizing hormone, or LH, helps build connections between neurons.

Dr. Gemma Casadesus views slides of brain tissue affected by Alzheimer's Disease. Her work has uncovered a previously unknown pathway in the brain for luteinizing hormone that promotes memory and cognition.
Credit JEFF ST.CLAIR / WKSU

“Basically what I think LH does," she says, "is it maintains the flexibility of a system that regulates learning, and memory,and cognition.”

And she thinks the lower levels of LH post menopause makes the brain more vulnerable to problems like Alzheimer’s.

Her work takes her far afield from the traditional targets of Alzheimer’s research, the protein known as amyloid beta that forms plaques on diseased neurons.

But she’s ok with that.

“The reality is that we’ve been focusing on amyloid beta for 30 years and we don’t have a clear explanation yet, so perhaps we might want to look at everything else.”

Casadesus envisions a time when hormone therapy may be part of Alzheimer’s prevention, but for now she says simple lifestyle choices are our best bet for avoiding the disease.

She says eat your fruits and vegetables, keep your brain active, and get enough exercise, because...

“What’s good for your body is good for your brain.”

Researchers agree that with a disease as complicated as Alzheimer’s it’s unlikely we’ll find one cause, or one cure.