Researchers at the RIKEN Center for Brain Science have discovered a mutation that can protect against Alzheimer’s disease in mice. Published in the scientific journal Nature Communications, the study found that a specific mutation can reduce the characteristic accumulation of the amyloid-beta peptide that occurs.

Pictured is the control (upper left) in the mouse model of AD with varying levels of the deleted gene (other three panels). Note that Aβ; plaques (green) were fewer as the percent of the deletion (ΔUTR) increased. Scale bar: 1 mm. © RIKEN National Science Institute

Despite several pathogenic mutations having been identified for Alzheimer’s disease, there has only been a single protective mutation found in humans. While this study uses a mouse model, it does present a potential candidate worthy of further investigation to better understand the pathogenic mechanisms of the disease.

One of the characteristics of Alzheimer’s is the accumulation of plaques between neurons. These plaques are made from amyloid-beta, a leftover part of the amyloid precursor protein (APP). APP itself has key roles in neuronal development, signalling, intracellular transport, and other aspects of neuronal homeostasis.

Using CRISPR, Takaomi Saido’s team created mice with a mutated APP gene. The result was a reduction in amyloid-beta accumulation in the mouse model of the disease. The technique used resulted in mice with varying levels of mutation to the APP gene. Interestingly, the level of reduction in amyloid-beta accumulation correlated with the level of inactivation of the APP gene.

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