A new approach that relies on subduing early events that occur in the brain long before symptoms of Alzheimer’s disease can help prevent or delay Alzheimer’s disease, finds a new study jointly undertaken by scientists at top research centres in the US — Baylor College of Medicine, Texas Children’s Hospital and Johns Hopkins University School of Medicine.
“Common diseases like Alzheimer’s, Parkinson’s and dementia are caused in part by abnormal accumulation of certain proteins in the brain,” says study senior author Dr. Huda Zoghbi, professor of molecular and human genetics at Baylor College of Medicine, a premier American academic health science centre based in Houston, Texas.
According to Dr. Zoghbi, some proteins become toxic when they accumulate in the brain. “They make the brain vulnerable to degeneration. Tau is one of those proteins involved in Alzheimer’s disease and dementia,” she says.
The study aimed at finding new ways to prevent or reduce tau accumulation in the brain. This could help uncover new possibilities for developing drug treatments for these diseases.
Earlier studies have focused mainly on the final stages of Alzheimer’s disease, says Dr. Cristian Lasagna-Reeves, postdoctoral fellow in Dr. Zoghbi’s lab.
“Here we tried to find clues about what is happening at the very early stages of the illness, before Clinical Irreversible Symptoms appear, with the intention of preventing or reducing those early events that lead to devastating changes in the brain decades later,” she adds.
The scientists were able to prevent those early events and the subsequent development of brain pathology in experimental animal models in the lab.
To find which enzymes affect tau accumulation, the study authors systematically inhibited enzymes called kinases.
“We inhibited about 600 kinases one by one and found one, called Nuak1, whose inhibition resulted in reduced levels of tau,” said Dr. Zoghbi.
The scientists screened the enzymes in two different systems, cultured human cells and the laboratory fruit fly. Screening in the fruit fly allowed them to assess the effects of inhibiting the enzymes in a functional nervous system in a living organism.
Screening such a large number cannot be done with other animal models like the mouse, and cultured cells cannot model complex nervous system functions, according to co-senior author Dr. Juan Botas, a professor at Baylor.
“Scientists in the field have been focusing mostly on the final stages of Alzheimer’s disease,” said first author Dr. Cristian Lasagna-Reeves, postdoctoral fellow in the Zoghbi lab. “Here we tried to find clues about what is happening at the very early stages of the illness, before clinical irreversible symptoms appear, with the intention of preventing or reducing those early events that lead to devastating changes in the brain decades later.”
The study, published recently in the prestigious Cell Press journal Neuron, assumes significance as in the future it might be possible to treat people at risk for Alzheimer’s disease by keeping tau low.