Researchers have shed new light on the nerve cell processes that lead to Alzheimer’s disease, overturning previously held ideas of how the disease develops and opening the door to new treatment options that could halt or slow its progression.

The study was published in the journal Science.

Studying human brain tissue, the research team identified a protein, kinase p38γ, that is lost as AD progresses. When they reintroduced the protein into the brains of mice, it was shown to have a protective effect against memory deficits associated with the disease.

Two of the hallmarks of Alzheimer’s are the presence of protein plaques (made up of amyloid-beta) and tangles (made up of tau protein) in the brain. The accumulation of these plaques and tangles is associated with cell death, brain atrophy and memory loss.

The research team revealed that a crucial step in the process that leads to tangles has been misunderstood. Previously, scientists believed the plaque-forming protein, amyloid-beta, caused a modification – called phosphorylation – to the tau protein resulting in cell death and, ultimately, Alzheimer’s disease. Increased phosphorylation of tau eventually leads to its accumulation as tangles.

Results from the new study suggest that the phosphorylation of tau initially has a protective effect on neurons, and that amyloid-beta assaults the protective functionality until it is progressively lost. This is the stage at which toxicity levels cause the destruction of neurons and results in the cognitive deficits associated with Alzheimer’s disease.

The study used different mice models and human brain tissue from the Sydney Brain Bank to identify a protein called kinase p38γ, which assisted the protective phosphorylation of tau and interfered with the toxicity created by amyloid-beta.

The next step for the researchers will be to develop their patented discoveries into a novel treatment for humans.

Paper: Site-specific phosphorylation of tau inhibits amyloid-β toxicity in Alzheimer’s mice”
Reprinted from materials provided by the University of New South Wales.