On 4 November, Joseph F. Arboleda-Velasquez and colleagues published a paper showing that a rare gene mutation may protect against the onset of symptoms in Alzheimer's disease (AD). Findings were published in the journal Nature Medicine. It is a single case report of a women in Colombia who carried the E280A mutation in the gene called PSEN1, which is known to cause early-onset AD. The woman was at high risk for early-onset AD and predisposed to develop AD in her forties but remained unimpaired until her seventies, three decades after the expected age of clinical onset.
In the published study, researchers analysed genetic data from a Colombian family with more than 6.000 living members. They identified about 1.200 individuals in the family who had the E280A mutation and developed mild cognitive impairment (MCI) at about 44 years old and dementia at 49 years old. They found that one women who carried the E280A mutation didn’t develop MCI until she was in her seventies. Like her relatives, she carried the E280A mutation and had large amounts of brain amyloid-beta deposits in her forties. However, she had limited tau tangles and minor neurodegeneration. Researchers suggested that she may have been protected because she had a rare mutation in the APOE gene, a gene associated with AD. Analysis showed that she was the only one who carried two copies of the APOE3 gene variant, named Christchurch. As the findings from this study relate to a single individual, further research is needed to understand the role of APOE in the pathogenesis, treatment and prevention of AD.
