LSU lab finds potential early red flag of Alzheimer’s in brain fluid

By the time symptoms of Alzheimer’s disease show up, changes in the brain have likely been happening for decades, and many scientists have concluded that treatment is too late to be helpful. But what if the clear, colorless fluid surrounding the brain could foretell the risk, acting as a red flag and a potential target for future drugs?

A team at LSU Health New Orleans has identified an inflammation-causing compound in cerebrospinal fluid that could act as an early identifier of Alzheimer’s, which is expected to affect 110,000 people in Louisiana by 2025.

Among patients with varying degrees of memory problems who participated in a study, published last week in the journal Cellular and Molecular Neurobiology, those with higher levels of the compound also had higher levels of cognitive problems. Study author Dr. Nicolas Bazan, a neuroscientist at LSU Health New Orleans, hopes to use that information to help define the true onset of Alzheimer’s.

“If we know the key changes in the human brain early on, we might be able to intervene therapeutically, to slow down the loss of memory,” Bazan said.

The samples of cerebrospinal fluid arrived at LSU from patients in Sweden, where they were collected by the Karolinska Institute in plastic foam coolers packed in dry ice. From there, Bazan's team placed 136 tiny vials in machines that extract the different components present in the fluid.

The team looked at the samples from three different groups:

• People with subjective cognitive impairment, in which patients have reported a difference in memory abilities but the problems are not severe enough to appear on cognitive tests
• People with mild cognitive impairment, defined as memory problems more severe than normal aging, often a precursor to dementia
• A group with a diagnosis of Alzheimer’s disease.

Two main findings stood out to researchers, who looked at 22 different lipids, or fats, that make up the cerebrospinal fluid. Compounds in the brain that help calm inflammation were low in people with the most severe memory loss. And in that same group, the compounds that promote inflammation were high.

In other words, the greater the severity of memory problems, the lower the level of the compound that resolves inflammation and the higher the level of the one that causes it.

Bazan, who sits on the board of the New Orleans Opera, thinks about these tiny compounds, known as lipid mediators, like a director conducting a symphony. All of the cells and components have to hit the right notes for brains to function properly. These lipid mediators keep the brain in balance. 

“Our brains require harmony,” he said. “This molecule prevents somebody from going off the script of the music, in a way.”

The connection between inflammation and brain disease has been increasingly identified as a driver of neurodegeneration, said Dr. Greg Bix, a Tulane University neuroscientist who was not involved in this study. It’s not surprising to find certain compounds associated with inflammation in the brains of people struggling with memory function. What’s new about this study, he said, is that it identifies specific factors that could act as biomarkers, or measures of disease progression.

“The simple goal with Alzheimer’s is to prevent it from occurring,” Bix said. “The trick is to catch it early, looking at biomarkers, which is really where the field is moving – to intervene early enough to prevent the process from happening.”

Bix also points out that lifestyle factors in early life or middle age help keep inflammation in check as people get older.

“A lot of these inflammatory factors are contributed to by a lack of activity, obesity, diabetes, that sort of stuff,” he said. “Persistent sleep deprivation can actually lead to an accumulation of junk in the brain that feeds back on inflammation.”

In the future, Bazan and his team hope to continue to study whether adding the lipid mediators that calm inflammation back into the brain might help keep it in harmony, which they have demonstrated in mice in another study published last month in Communications Biology, a Nature journal. He sees it as one potentially illuminating piece of a puzzle that has gone unsolved for decades. 

“I believe this is a key driver of the puzzle,” Bazan said. “But there are others, also.”

To learn more, visit nola.com