Alzheimer’s Disease: Exploring the Icelandic Pathway

An intriguing discovery was made in 2012 within the Icelandic population, revealing a mutation that provides a protective effect against Alzheimer’s disease. This mutation, known as “A673T,” is found in less than 1% of Scandinavian populations and is located on a gene that encodes a precursor protein of amyloid (APP in English).

Alzheimer’s disease affects approximately one million people in France and is characterized by the accumulation of amyloid protein plaques in the brain, as well as tau proteins in the neurons themselves, making them the main therapeutic targets. In a study published in Molecular Psychiatry on June 14, a French team describes how they were able to partially halt this mechanism in mice by leveraging the discovery made by an Icelandic team in 2012.

The disease is sometimes considered in the model of prion diseases, where a protein with an abnormal conformation gradually induces the same three-dimensional structure and eventually forms harmful aggregates. Researchers are exploring the hypothesis of “pseudo-prions,” where certain APPs trigger this domino effect. The effects of different strains of APP, such as the Icelandic strain, are being investigated for their potentially protective effects.

To test this, researchers injected a peptide derived from the APP, carrying the A673T mutation, into the hippocampus of transgenic mice designed to mimic Alzheimer’s disease. The hippocampus, a brain structure heavily involved in memory, showed reduced inflammation, tau protein accumulation, synaptic damage, and cognitive impairment. Memory, in particular, was protected, with a single injection producing lasting effects for up to nine months.

Researchers are now looking at how these results can be translated to humans. At Laval University in Quebec, Jacques Tremblay is working on a gene therapy approach using molecular scissors like Crispr-Cas9 to introduce the beneficial Icelandic mutation directly into the genome of neurons. The promising results from the mouse models are encouraging further exploration into potential human applications.

These findings open up new possibilities for the treatment and prevention of Alzheimer’s disease, offering hope for the future. The road ahead involves further research and clinical trials to determine the safety and efficacy of these potential therapies in humans. The field of neuroscience continues to evolve, bringing us closer to understanding and combating neurodegenerative diseases like Alzheimer’s.