Rare gene variant delays onset of Alzheimer's disease

An uncommon genetic variant delays the age of onset for carriers at risk from developing early-onset Alzheimer's disease.

US scientists have discovered that having only one copy of the APOE3 Christchurch gene variant delays cognitive decline in people who carry the unrelated Paisa mutation, which usually leads to early-onset Alzheimer's disease. The Christchurch variant was shown to reduce the onset of dementia symptoms by five years in those patients at risk.

'Our new study is significant because it increases our confidence that this target is not only protective, but druggable,' senior author Dr Joseph Arboleda-Velasquez, from the Schepens Eye Research Institute in Boston, Massachusetts, told the Independent. 'We think that therapeutics inspired by protected humans are much more likely to work and to be safer.'

The study published in the New England Journal of Medicine, led by the Massachusetts General Hospital, the Schepens Eye Research Institute, and Banner Alzheimer's Institute, studied whether the age of onset could be influenced by the Christchurch variant, previously thought to be protective against Alzheimer's disease.

Researchers investigated 27 participants with one copy of the Christchurch variant, out of 1077 carriers of the Paisa mutation, all relatives from the Antioquia region in Colombia. Participants without the Christchurch variant were also compared, to estimate the age of onset when dementia symptoms first occurred. The median age of onset for carriers of the Christchurch and Paisa variants was 52 years compared to 47 years for those with the Paisa mutation alone.

Of the participants with both variants, two patients underwent brain imaging and a further four underwent post-mortem analysis. The brain scans showed preserved metabolic activity in the brain regions prominently affected by Alzheimer's disease. The post-mortems unveiled fewer beta-amyloid plaques – one of the defining features of Alzheimer's disease – in the blood vessels compared to deceased Paisa carrier brains without the Christchurch mutation.

'As a clinician, I am highly encouraged by our findings, as they suggest the potential for delaying cognitive decline and dementia in older individuals,' lead author, Dr Yakeel Quiroz, from the Departments of Psychiatry and Neurology at Massachusetts General Hospital, told the Independent. 'Now we must leverage this new knowledge to develop effective treatments for dementia prevention.'