A team of international researchers has identified 75 regions of the genome that are associated with Alzheimer’s disease in the largest study of genetics in the neurodegenerative disorder to date.
The study, New insights into the genetic etiology of Alzheimer’s disease and related dementias published in Nature Genetics, has identified 42 new genes that appear to be connected to the disease, increasing the total number linked to Alzheimer’s to 75. The discovery has the potential to open up new channels of research for diagnosis and treatments.
In particular, the findings look at disruption to innate immunity – the first line of defence against pathogens – as well as overly aggressive activity of white blood cells in the central nervous system called microglia.
Alzheimer’s disease is a chronic neurodegenerative disorder and is the most common form of dementia, affecting more than 26 million people worldwide. There is no treatment available to improve the progressive course of the condition, but progress in human genome analysis is leading to further advances in this area.
The disease, which typically develops after the age of 65, has a strong genetic component. Many cases are believed to be caused by the interaction of different genetic predisposition factors with environmental factors, such as diet and lifestyle.
Another significant finding is the role the tumour necrosis factor (TNF) alpha-dependent signalling pathway plays in the disease. Treatments that restrict TNF are already widely used to treat inflammatory diseases, including Crohn’s disease, rheumatoid arthritis and psoriasis.
The findings also validated the importance of amyloid beta and tau proteins, which have been under scrutiny during the drug discovery efforts in Alzheimer’s over the last two decades.
The researchers created a genetic risk score that they believe could predict which patients with cognitive impairment will develop Alzheimer’s within three years.
Professor Jean-Charles Lambert, research director at France’s National Institute of Health and Medical Research at Inserm, led the international team of researchers from France, the UK, the US and other European nations.
Professor Lambert said the discovered genes are being assessed to “give them meaning in relation to our clinical and biological knowledge, and thereby gain a better understanding of the cellular mechanisms and pathological processes at play”.
He added: “While this tool is not at all intended for use in clinical practice at present, it could be very useful when setting up therapeutic trials in order to categorise participants according to their risk and improve the evaluation of the medications being tested.”