An international study involving researchers from Massachusetts General Brigham Hospital has revealed that one copy of a protective genetic variant could delay the early onset of Alzheimer’s disease (AD).
Findings from the study published in the New England Journal of Medicine add new evidence to develop a potentially new therapeutic target for the neurodegenerative condition.
Currently the most common form of dementia, which affects 900,000 people in the UK, AD is a brain disorder that progressively destroys memory, thinking skills and eventually the ability to carry out simple day-to-day tasks.
Previous research carried out in 2019 from two Mass General Brigham hospitals, Mass Eye and Ear and Massachusetts General Hospital, reported two copies of a rare variant of the APOE3 gene called Christchurch (APOE3Ch) in a patient who did not develop cognitive impairment until her late 70s, despite having a high genetic risk for developing early-onset AD.
Building on this, researchers examined a genetic variant called Presenilin-1 E280A (Paisa), an autosomal dominant variant that can cause a genetic condition if inherited from a parent, particularly AD, which consists of around 6,000 blood relatives, around 1,200 of whom carry the Paisa variant.
The team assessed 1,077 descendants of the Colombian family, identifying 27 family members who carried both the Paisa mutation and one copy of the Christchurch variant and performed functional brain imaging scans on two individuals, which showed lower levels of tau and preserved metabolic activity in areas typically associated with AD.
In addition, the team analysed autopsy samples from four deceased individuals that showed less pathology in blood vessels, which is a key characteristic of the protective qualities of APOE3Ch.
The findings provide evidence that having one copy of the APOECh could induce a level of protection against AD and offer the potential for drug development by targeting this genetic pathway.
Joseph Arboleda-Velasquez, associate scientist, Mass Eye and Ear, commented: “Our original study told us that protection was possible and that was an important insight.
“Our new study is significant because it increases our confidence that this target is not only protective but druggable.”