Van Earl Wright, Scotland Wright, Alice Wright-Stephens, and Bryant Wright. “That was just real sad grief for me, a lot of crying time,” Wright-­Stephens said of her experience watching her mother, Beth, decline. Beth died in 2013 from Alzheimer’s disease, and their father now has the same illness. Photo: Christopher Moore.

The Wrights

Chances are, if you reach your golden years, you or someone close to you will get Alzheimer’s — like the late Beth Wright and her husband, George, who now requires 24-hour care.

Their children — Alice, an etiquette teacher; Bryant Wright, an ­Atlanta-area pastor; Van Earl Wright, a TV sportscaster; and Scotland Wright, a business owner — hope that by sharing touching and harrowing moments from their parents’ decline, they can help others who are caring for loved ones with Alzheimer’s. Their accounts are interspersed in the following segments on current research.

Healthy Brain vs. Severe Alzheimer's Alzheimer’s kills so many neurons (core nerve cells) that it riddles the brain with gaping crevasses and can remove 30 percent of its total mass, debilitating mental functions. Image: National Institute on Aging, National Institutes of Health.

Alzheimer’s kills so many neurons (core nerve cells) that it riddles the brain with gaping crevasses and can remove 30 percent of its total mass, debilitating mental functions. But in the beginning, it can move slowly and cause momentary memory lapses or personality breakdowns, like those that beset Beth.

“There was an elegance about her, a genteelness about her,” Bryant recalled. “She was the consummate Southern lady, and so gracious,” Scotland said.

But suddenly, their mother began blowing up in rage, and extreme fear displaced her inborn self-confidence. “It was so opposite of the person we were reared by,” Van Earl said. “I remember us being on conference calls. We didn’t know what was going on.”

Square one

In 1906, Dr. Alzheimer autopsied Deter’s brain. Examining the tissue under the microscope, he found two characteristics that became the pillars of official Alzheimer’s diagnosis. “One was amyloid plaque, and the other was neurofibrillary tangles,” said Dr. Allan Levey, director of the Emory Alzheimer’s Disease Research Center.

Both the plaque, which is outside the neurons, and the tangles, which are inside them, are made of protein molecules that naturally exist in the brain, but they appear to have gone wrong. The amyloid beta plaque, in particular, forms scruffy, large clumps, and researchers have been fixated on it as the cause of Alzheimer’s for decades, resulting in a single-minded drug-development approach.

“The bias has been enormous,” Levey said. “Bias is a very conservative word in this example.”

Drugs focusing on removing amyloid beta plaque have all failed so far. “We’re now looking at a disease that is one of the leading causes of death, for which we don’t have a single treatment,” he said.

Research has sunk billions of dollars, and one failed drug can financially ruin a drug maker. “Many of the biggest pharmaceutical companies have gotten out of the Alzheimer’s business,” Levey said.

It’s time to go back to square one, he said, and really figure out what’s causing this disease.

Data detective

To guide future research, Levey would especially like to see the data collected in countless studies mined to sort the wheat from the chaff.

Cassie Mitchell does just that. The informaticist at the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University has combed thousands of studies focused on the proteinaceous amyloid beta plaque and fibrillary tangles, which are made of a protein called tau, to mine suitable datasets for clearer associations with cognitive decline.

Cassie Mitchell (right), an informaticist at the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, has combed thousands of studies focused on amyloid beta plaque and fibrillary tangles. Photo: Rob Felt.

In the composite data, amyloid beta plaque has not looked like a fruitful treatment target.

“When you pull everybody’s data together, there’s no correlation that can be seen through all the data,” Mitchell said. In other words, across masses of data, high levels of amyloid beta plaque in a brain do not correspond to more mental decline. (Alzheimer’s lab studies are based on models of diseased brains in mice.)

But data analyses look very different for the protein behind the fibrillary tangles — that tau, particularly “phosphorylated” tau, or p-tau. “There’s a very strong correlation with mental decline,” Mitchell said. “We need to look more into how p-tau fits into the picture.”

Phosphorylation is a normal part of cell life that makes protein molecules more chemically active, but in Alzheimer’s, too much tau gets phosphorylated, Mitchell said, and that may create those tangled fibrils inside of neurons.

Prion problems

Yury Chernoff agrees with the take on p-tau but has a slightly different assessment of amyloid beta.

He studies proteins gone bad, particularly prions, which are widely known as the cause of mad cow disease, which, like Alzheimer’s, destroys the brain. Chernoff implants human amyloids in yeast cells to experiment with them, and he firmly believes that bad versions of the protein are indeed the cause of Alzheimer’s disease, the way prions are the cause of mad cow disease.

“The whole mechanism is very similar to a lot of proteins which occur in different diseases and different organisms,” said Chernoff, a professor in Georgia Tech’s School of Biological Sciences.

But Mitchell’s conclusions make sense to him. Having amyloid beta bound up in clunky plaque wads might make it less able to enter neurons and damage tau. He has seen similar scenarios in which harmful proteins became less harmful as their accumulations grew.