Discovery of immune system genes that trigger Alzheimer’s disease
The complex nature of Alzheimer’s disease (Alzheimer’s) is known to be caused by the abnormal accumulation of amyloid and tau proteins in the brain, whereby several genomic regions associated with amyloid and tau production can influence risk of disease progression and severity.
In a new landmark study, an international team of researchers pinpoint new genetic pathways that traditionally play a role in immune system functions – particularly those that influence microglial activity, a type of central nervous system immune cell. Microglia are responsible for clearing out damaged tissue, but a lack of microglia could accelerate Alzheimer’s, said Professor Julie Williams from the UK Dementia Research Institute, Cardiff University.
In the study, 30 years’ worth of genomic data from 111,326 Alzheimer’s patients was pooled and compared to a control group of 677,663 healthy subjects. At the end, 75 genomic regions associated with Alzheimer’s disease were found, 33 of which were previously known and 42 that were new discoveries.
Of the new regions, the researchers identified an inflammatory pathway involving an immune protein known as TNF-alpha which was genetically linked to Alzheimer’s risk. This is the first time that TNF-alpha has been implicated in the development of the disease.
The study findings also hinted at the predictive capacity of the genetic associations – more precisely, a genetic risk score could be calculated, with predictions close to 84% accuracy of whether a patient experiencing mild cognitive impairment would progress to Alzheimer’s disease within three years.
Although individual risk evaluation based off genetic studies can yet be applied to clinical practice, Susan Kohlhaas, Director of Alzheimer’s Research UK, said the findings remain a potent reminder of just how complex Alzheimer’s disease is, and how different combinations of genetics and environment can trigger the disease.
“Creating an extensive list of Alzheimer’s disease risk genes is like having the edge pieces of a puzzle put together, and while this work doesn’t give us the full picture, it provides a valuable framework for future developments,” Kohlhaas explained. “The research also tells us just how complex Alzheimer’s is, with several different mechanisms implicated in the development of the disease.”
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