A “pseudo-prion” molecule protects the brain from Alzheimer’s disease in mice
Research
On June 18, 2024
A research team, involving scientists from Grenoble Institut des neurosciences (GIN - CEA/CHUGA/Inserm/UGA) and Laboratoire des maladies neurodégénératives (CNRS/CEA/Université Paris-Saclay), has discovered that the injection of a modified “pseudo-prion” protein into the brains of mice could protect the animals against Alzheimer’s disease, a pathology that currently affects nearly a million people in France.
This neurodegenerative disease originates from lesions caused by an abnormal accumulation in the brain of two proteins: amyloid-β and Tau. These lesions damage neurons and their synapses, ultimately causing an inability to create new memories.
To block these processes, the scientists injected a mutated amyloid-β protein (Icelandic mutation) into the brains of mice that model the disease. This very rare protein, called amyloid-βice, had been discovered in certain individuals of Icelandic origin who presented with improved cognitive ageing and never developed Alzheimer’s disease.
The results were surprising: the synapses returned to their normal state and there were no memory losses characteristic of the disease. Administration of this modified protein[1] thus protected the brains of the mice against all the malfunctions related to the disease. Furthermore, the scientists showed that a single dose was sufficient to trigger this protection, which remained active for several months.
The scientific community had previously agreed to the hypothesis that the administration of amyloid-β proteins could only amplify the pathology because they behave like “pseudo-prion” proteins[2]. This new study published on 14 June 2024 in Molecular Psychiatry, shows for the first time in mice that “pseudo-prion” amyloid-β proteins can protect the brain against the damage characteristic of Alzheimer’s disease. These findings could thus provide a starting point for a new category of preventive therapies to treat people with early-stage neurodegenerative diseases and block the course of the disease, thanks to the injection of protective prions.
To block these processes, the scientists injected a mutated amyloid-β protein (Icelandic mutation) into the brains of mice that model the disease. This very rare protein, called amyloid-βice, had been discovered in certain individuals of Icelandic origin who presented with improved cognitive ageing and never developed Alzheimer’s disease.
Visualisation of a brain with an amyloid-β filament. In blue, the position of the Icelandic mutation protecting against Alzheimer’s disease. © : Luc Bousset, Marc Dhenain
The results were surprising: the synapses returned to their normal state and there were no memory losses characteristic of the disease. Administration of this modified protein[1] thus protected the brains of the mice against all the malfunctions related to the disease. Furthermore, the scientists showed that a single dose was sufficient to trigger this protection, which remained active for several months.
The scientific community had previously agreed to the hypothesis that the administration of amyloid-β proteins could only amplify the pathology because they behave like “pseudo-prion” proteins[2]. This new study published on 14 June 2024 in Molecular Psychiatry, shows for the first time in mice that “pseudo-prion” amyloid-β proteins can protect the brain against the damage characteristic of Alzheimer’s disease. These findings could thus provide a starting point for a new category of preventive therapies to treat people with early-stage neurodegenerative diseases and block the course of the disease, thanks to the injection of protective prions.
Treatment with Aβice pseudo-prions reduces the toxic lesions of Alzheimer’s disease, protects brain cells from the disease and thus protects memory. © Marc Dhenain / CNRS
1. The proteins administered were created artificially in the laboratory.
2. Abnormal prion proteins are generally responsible for severe neurodegenerative diseases such as mad cow disease or Creutzfeldt-Jakob disease. Their normal form is naturally present in our brains. However, when a prion protein changes shape it becomes abnormal and then other surrounding proteins adopt the same abnormal shape, thus amplifying the processes under way. Amyloid-β protein can also behave in this way, so it is considered as a “pseudo-prion”.
2. Abnormal prion proteins are generally responsible for severe neurodegenerative diseases such as mad cow disease or Creutzfeldt-Jakob disease. Their normal form is naturally present in our brains. However, when a prion protein changes shape it becomes abnormal and then other surrounding proteins adopt the same abnormal shape, thus amplifying the processes under way. Amyloid-β protein can also behave in this way, so it is considered as a “pseudo-prion”.
Published on June 19, 2024
Updated on June 19, 2024
Updated on June 19, 2024
Bibliography
Transmissible long-term neuroprotective and precognitive effects of 1-42 beta-amyloid with A2T Icelandic mutation in an Alzheimer’s disease mouse model.
Marina Célestine, Muriel Jacquier-Sarlin, Eve Borel, Fanny Petit, Fabien Lante, Luc Bousset, Anne-Sophie Hérard, Alain Buisson, et Marc Dhenain.
Molecular Psychiatry, June 14, 2024.
Marina Célestine, Muriel Jacquier-Sarlin, Eve Borel, Fanny Petit, Fabien Lante, Luc Bousset, Anne-Sophie Hérard, Alain Buisson, et Marc Dhenain.
Molecular Psychiatry, June 14, 2024.
