A Protein Might Lead To Dementia, But We Could Slow It

Types of dementia like Alzheimer’s disease have long been linked to a buildup of amyloid plaques and tau tangles in the brain. These are both proteins that have been compared to the “trigger and bullet” in the development of the condition.

But in a new study, researchers focused on a less-investigated protein: GRK2.

This research found that GRK2 has two different forms, with one kind especially plentiful in the minds of those with dementia.

Not only did they identify this problematic protein, but in tests conducted on mice, the scientists seemed to be able to block its effects.

About 20 years ago, the study’s lead author, Professor Ursula Quitterer, was sent brain tissue removed during tumour surgery. These samples came from people both with and without dementia.

There are two forms of GRK2: an active and an inactive kind. During extensive research both on the aforementioned tissue samples and on mice, Prof Quitterer and her team found that the brains of people with dementia had a lot more inactive GRK2 than those without.

During the development of dementia, inactive GRK2 deposits onto brain cells and damages their mitochondria (the energy-generating “powerhouse” of the cell). These “aggregates block the pores of the mitochondria, reducing the amount of energy they can supply and leading to a situation of stress inside the cells,” Prof Quitterer said.

In mouse studies, higher levels of inactive GRK2 were also linked to the accumulation of amyloid plaques. As we mentioned above, these have long been suspected to play a role in the development of dementia.

Worse, the stress amyloid plaques place on brain cells may lead them to form more inactive and clumping GRK2 – potentially creating a vicious cycle.

Prof Quitterer and her colleagues created a variety of chemical compounds to try to stop these inactive GRK2s from having such a negative effect on the brain.

After trials on both mice and human tissue samples, their “Compound 10” creation performed the best. It stopped GRK2 from aggregating, meaning mitochondria could keep doing their job.

And the brain’s nerve cells seemed more able to keep their function and stay alive, too.

Prof Quitterer, who is currently awaiting a patent for Compound 10, added: “Alzheimer’s is a very complex disease. That’s why it’s so important that we’ve now identified a new target protein in the form of GRK2, as well as an active ingredient that operates via GRK2 and therefore via a different mechanism than existing Alzheimer’s drugs.”