An obscure enzyme named HDAC9 may be a key to understanding the origins and prevention of Alzheimer’s Disease and dementia in general.

At Augusta University, researchers found that the amount of the enzyme we have drops as we age and is particularly scarce in people who develop Alzheimer’s and dementia. The scientists theorize that the enzyme is involved in keeping neurons healthy.

HDAC9 is part of a group of enzymes that control how tightly DNA strands are wrapped, which impacts gene expression.

Now the new study has found evidence that the same enzyme may be vital to the way that neurons communicate.

A key clue: the only place in the body where the enzyme is produced is in brain cells, especially in the hippocampus and prefrontal cortex, the parts of the brain where learning and memory are centered.

In studies using mice, the research team found lower levels of HDAC9 in rodents showing Alzheimer’s-like symptoms than in those who didn’t. 

Also, the enzyme’s level dropped abnormally before Alzheimer’s telltale amyloid proteins began to clog the brain. That could offer a blood test indicating Alzheimer’s is in a person’s future, allowing treatment to begin early.

At University College London, researchers injected a protein called “klotho” into elderly rhesus monkeys. The injections improved the monkeys’ ability to remember where they had previously found food—an achievement the researchers likened to remembering where you left your car in a parking lot.

Before the single injection, the monkeys could remember where the food was 45 percent of the time.  After the one-and-done treatment, they remembered 60 percent of the time. The memory boost lasted for a minimum of two weeks.

The scientists found that klotho injections improved communication among brain cells.

Klotho occurs naturally in mammals, including humans, but as we age the body produces less of it.

Klotho as it occurs naturally has been shown to stimulate growth processes in tissues and inhibit cancer tumors. Using mice, earlier studies had shown that over-expressing the gene that makes klotho extended mice’s lives by as much as 30 percent.

In humans, a study from the Norwegian University of Science and Technology found that people with Alzheimer’s had lower levels of klotho in their blood than people without the disease.

However, a key mystery remains: klotho is unable to cross from the bloodstream into the brain, so researchers have no clear idea how it boosts memory.

While that question is being explored, researchers say the effects of boosting klotho are clear enough to warrant beginning human trials.

TRENDPOST: Next steps for HDAC9 will include finding out what other substances in the brain might influence HDAC9’s presence and actions.

Eventually, treatments for Alzheimer’s and dementia could be formulated based on increasing the amount of HDAC9 in the brain or klotho in the bloodstream. 

Delivery for HDAC9 will be the key: if the enzyme is made only in the brain, it might not be able to cross from the bloodstream to the brain if injected into a vein. 

Scientists also will be looking for a way to nudge the brain and body to produce more of the two substances on their own.

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