Drinkable cocktail shows promise interfering with crucial step of Alzheimer’s

Yale researchers have identified designer molecules to target damaging prion protein interactions



Natasha Taylor
01/08/2019

Yale researchers have identified a drinkable cocktail of designer molecules which interfere with a crucial first step of Alzheimer’s disease. The compound was even shown to restore memories in mice in recent tests.

Amyloid-beta peptides, the hallmark of Alzheimer’s, couple with prior protein at the surface of brain cells and transmit damaging instructions to the interior of the cell. This leads to a number of effects, such as the accumulation of plaques, a destruction immune system response and damage to the synapses. 

The team sought a molecule to interfere with damaging prion protein interactions with amyloid beta, finding success with an old antibiotic

In their efforts to find molecules that may have a therapeutic effect on this network, Stephen Strittmatter, Director of the Yale Azheimer Disease Research Center, and Erik Gunther screened tens of thousands of compounds. The team sought a molecule that could directly interfere with the damaging prion protein interaction with amyloid beta.

They discovered an old antibiotic to be a promising candidate; however it was only active after decomposing to form a polymer. Related small polymers retained the benefit and also managed to pass through the blood-brain barrier.

Once the optimized polymeric compound was dissolved, it was fed to mice engineered to have a condition which mimics Alzheimer’s. During the course of treatment, they found that synapses in the brain were repaired and mice recovered lost memory.

A collaborating team at Dartmouth University reported a positive response when delivering the same cocktail to cells modeled to have Creutzfeldt-Jakob Disease, a devastating neurological condition caused by infections with misfolded prior protein.

The treatment has also shown a positive response in cell tests for Creutzfeldt-Jakob Disease

Alzheimer’s disease affects 5.7 million Americans, and that number is expected to reach 14 million by the year 2050. To date, most of the research on the disease’s effects on the brain has been done postmortem. To investigate new treatments, researchers have recently explored methods for measuring memory loss in living patients.

The next step for the Yale team is now to verify the compounds which aren’t toxic in preparation for the translation to clinical trials for Alzheimer’s disease.