New genetic cause of Alzheimer's disease identified

Research has found that having two copies of a gene variant known to increase the risk of developing Alzheimer's disease, may actually cause the disease.

The variant APOE4 was discovered over 30 years ago, and its impact on increasing the risk of developing Alzheimer's disease is well documented. However, the authors new research, published in Nature Medicine, suggest that viewing being homozygous for APOE4 – having two copies of the variant – is sufficient to cause Alzheimer's, representing a distinct genetic form of disease.

'Now we know that virtually all individuals with this duplicated gene develop Alzheimer's biology,' said the study's first author, Dr Juan Fortea, from the Sant Pau Memory Unit in Barcelona, Spain. 'This is important because they represent between two and three percent of the population.'

His colleague Dr Alberto Lleó, director of the Neurology Service at the same hospital, addied that 'the data clearly show that having two copies of the APOE4 gene not only increases the risk, but also anticipates the onset of Alzheimer’s, reinforcing the need for specific preventive strategies.'

The study analysed clinical data from more than 10,000 people, finding that almost all the 519 individuals homozygous for APOE4 developed Alzheimer's pathology relatively early in life, with symptoms emerging at an earlier age compared to other forms of Alzheimer's. Postmortem results from donated brains of over 3000 people similarly revealed that nearly all the 273 donors homozygous for APOE4 showed signs of Alzheimer's in the brain.

They concluded that virtually everyone with two copies of APOE4 will develop Alzheimer's if they live long enough.

These findings could impact the development of gene-targeted therapies aimed at mitigating the genetic risk associated with APOE4 and support the need for clinical trials to include individuals homozygous for APOE4 in the future.

It could also empower individuals to receive early diagnoses through genetic testing for APOE4, although Professor Jonathan Schott, chief medical officer at Alzheimer's Research UK, said that they do not currently advise that people have APOE genetic tests except if taking part in research, but that this advice could change in future.

Dr Richard Oakley, Alzheimer's Society's associate director of research and innovation, added: 'Dementia is the UK's biggest killer and this new insight into the role of genes shows there is still a lot to learn about this devastating disease'.