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Key gene associated with Alzheimer's disease identified

26 April 2021
Appeared in BioNews 1092

Researchers have identified a new key gene linked to the progression of memory loss in Alzheimer's disease.

Five genes of interest associated with Alzheimer's disease progression were identified and published in Nature Communications. One of these genes, SERPINA5, was correlated with an increase in protein tangles which are a key feature of the disease. Further investigation from these results could lead to treatments that may slow Alzheimer's disease progression.

Lead author Dr Melissa Murray from the Mayo Clinic in Jacksonville, Florida, suggested that these results mean 'we may have targets that indicate why some people have relative preservation and some people have relative exacerbation of memory loss symptoms.'

The researchers studied 385 tissue samples from brains of people who were diagnosed with Alzheimer's disease, that were donated to the Mayo Clinic Brain Bank. Importantly, these samples were from people who did not have any other brain disease, except Alzheimer's. This enabled the team to solely focus on targets applicable to the disease.

Firstly, the researchers studied the pattern of protein tangles that was associated with Alzheimer's, and from there they measured the gene changes that were responsible for instructing the proteins.

Finally, a machine learning algorithm was used that allowed the researchers to focus on five genes of interest, with the gene SERPINA5 most strongly associated with tau tangle progression, which abnormally accumulates in the brains of people with Alzheimer's disease. Their investigation focused on the hippocampus, the area of the brain responsible for learning and memory.

These results could help in understanding the reducing memory loss associated with the disease and how this disease affects patients across age and gender. The researchers plan to further investigate how SERPINA5 interacts with the protein tau.

'We hope to take a step back to look at a new interacting partner that may be actually accelerating tau or pushing tau accumulation past the tipping point' said Dr Murray. 'While we have direct evidence of SERPINA5 in the context of Alzheimer's disease, SERPINA3 in this same family of genes has also been looked at in Alzheimer's, and SERPINA1 in ALS. So I think it's about collective awareness and paying attention to this group of proteins.'

Abnormal tau accumulation has long been identified as a key contributor to Alzhiemer's disease and other neurodegenerative disorders. These results could help in understanding why and how tau accumulates, and may lead to future treatments to slow or halt dementia.

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