'INSTIGATOR' GENE ASSOCIATED WITH ALZHEIMER'S DISEASE DISCOVERED
In a new paper published in Nature communications, Mayo Clinic researchers and collaborators report the protein-coding gene SERPINA5 may worsen tau protein tangles, which are characteristics of Alzheimer's disease and advance disease. The researchers used samples from 385 brains donated to the Mayo Clinic Brain Bank, which houses more than 9,000 brain tissue specimens for the study of neurodegenerative disorders.
The samples were from people who were diagnosed with Alzheimer's disease and lacked co-existing diseases found in the brain. These samples were used to classify the pattern of protein tangles associated with Alzheimer's. Then the team used digital pathology and RNA sequencing to identify gene expression in the samples, which effectively measures gene changes responsible for instructing proteins.
Using a machine learning algorithm, the authors narrowed the genes of interest from about 50,000 to five. The top candidate, SERPINA5, was found to be strongly associated with tau tangle progression in the hippocampus and the cortex of the samples.
The team was recently awarded a grant by the state of Florida to ensure the findings are broadly applicable across on ethno-cohort, as the need for more research to clarify the relevance of gene expression changes on hippocampal vulnerability may be critical for preserving memory loss in Alzheimer's disease. But, Dr. Melissa Murray, Ph.D., a Mayo Clinic translational neuropathologist and lead author on the paper, says, by starting with the human brain and ending with it, the researchers hope their findings provide a deeper level of understanding that helps advance findings to clinical trials faster''.
''While we have direct evidence of SERPINA5 in the context of Alzheimer's disease. SERPINA1 in ALS. So I think it's about collective awareness and paying attention to this group of proteins''. Selective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer's disease, however, the degree of involvement of the different brain regions differs among patients.
This study highlights the importance of embracing heterogeneity of the human brain in diseases to identify disease-relevant gene expression.
