As he looks back on this year’s activities at the Rocky Mountain Alzheimer’s Disease Center, Huntington Potter, PhD, points to one event that was especially meaningful—receiving the center’s first brain donation for research from a person with Down syndrome who died with late-stage Alzheimer’s disease.

It’s a contribution neuroscience researchers hope will help further unravel the mystery of why some people develop Alzheimer’s disease symptoms while others do not.

Potter, whose groundbreaking research expanded knowledge of the genetic and molecular relationships between Alzheimer’s disease and Down syndrome, said the donation was made by a Denver-based family who felt that their sister would have been thrilled to know that she was making a significant contribution to science.

‘Great contribution’

And, Potter said, it’s a sentiment that goes beyond this one family. “People with Down syndrome and their families would very much like to help research to understand Alzheimer’s disease in them and in the rest of us, and so brain donations from people with Down syndrome are very important.”

“It’s a great contribution to humanity,” he added.

Potter plays multiple roles related to Alzheimer’s disease and Down syndrome research at the CU School of Medicine. In addition to being the Director of the Rocky Mountain Alzheimer’s Disease Center, he is also the Director of Alzheimer’s Disease Research at the Linda Crnic Institute for Down Syndrome.

The brain came from a 63-year-old woman named Gretchen Josephson, whose family has a long lineage in medicine and a connection to the CU School of Medicine.

Connection to Alzheimer’s disease

The direct link between Down syndrome and Alzheimer’s disease is on human Chromosome 21. People with Down syndrome are born with three copies of Chromosome 21 in every cell, a condition that occurs at conception.

Additionally, the main gene that produces the protein linked to Alzheimer’s disease resides on Chromosome 21. Because people with Down syndrome have this third copy of Chromosome 21 in all of their cells, Potter says that they all will develop the underlying Alzheimer’s disease pathology by the time they are 40 years old.

According to Potter, the mystery is that despite all people with Down syndrome having this predisposition to Alzheimer’s disease brain pathology, around 20% will not develop dementia symptoms.

“We’d like to study them to better understand how Alzheimer’s disease brain pathology and dementia develop,” he said. “That way, we could learn who is most likely to develop dementia and who isn’t. And we’d like to be able to initiate treatment for people who don’t have Down syndrome but who might be at risk, say, in their 40s or 50s, and prevent the cell death and the problems that accompany Alzheimer’s disease.”

Potter points out that Alzheimer’s disease is believed to start developing as many as 20 years before clinical symptoms appear. He says the main research goal is to develop treatments for people “on the steps” to Alzheimer’s disease, and also to develop early diagnoses.

The vast majority of people who are diagnosed with typical age-related Alzheimer’s disease, over 95%, do not have Down syndrome. However, Potter’s earlier research showed that they have Down syndrome-like cells with three copies of Chromosome 21 throughout their bodies, including in neurons in their brains.

Insights into the pathology

“What are the earliest signals in people with Down syndrome that they’re going to develop Alzheimer’s disease within 5 or 10 years? Can we use those same signals, whether it be a blood protein or a neuropsychological test, to help figure out when and whether the rest of us are at risk for Alzheimer’s disease?”

In recent years, Alzheimer’s disease research centers around the world have received many brain donations from typical people with Alzheimer’s disease, but not from people with Down syndrome. These donations are very rare, and “are very valuable,” said Potter, “because if we can understand more about the pathology that develops in people with Down syndrome, we will be better able to understand the pathology that happens in typical people. And that’s going to give us a hint of what’s going wrong, and of how we might be able to compare the brains and come up with an idea for fixing them.”

Potter also notes that receiving a brain for research from a person with Down syndrome who did not have dementia at death would be especially rare and would be extremely valuable for research.