Colombian Family Genes May Hold Key to Slowing Alzheimer’s Disease | Lifestyle

• Gene mutation may protect against Alzheimer’s disease

• 28 members of Colombian family with Christchurch mutation of APOE3 have delayed onset of Alzheimer’s disease

• This happened despite the presence of other mutations that would cause early-onset Alzheimer’s disease.

THURSDAY, June 20, 2024 (HealthDay News) — A genetic study of a Colombian family is shining a spotlight on a gene that may help protect people from the ravages of Alzheimer’s disease.

According to the researchers, about 1,200 of the 6,000 family members carry a genetic mutation called the “paisa mutation,” which causes early Alzheimer’s disease.

But 28 family members with the Paisa mutation avoided early Alzheimer’s because they carry another gene that protects against the degenerative brain disease, researchers announced June 20. New England Journal of Medicine.

The researchers say the study is the first evidence that carrying this alternative gene, known as the “Christchurch variant”, may confer some protection against inherited forms of Alzheimer’s disease.

Drugs and therapies that target this genetic pathway may be able to prevent or treat dementia and Alzheimer’s disease, said co-lead author Yakiel Quiroz, director of the Familial Dementia Neuroimaging Laboratory at Massachusetts General Hospital.

“As clinicians, we are very encouraged by the findings of this study, which suggest the possibility of slowing cognitive decline and dementia in older adults,” Quiroz said in a hospital news release. “Now we must use this new knowledge to develop effective treatments to prevent dementia.”

The study focused on mutations in the apolipoprotein E (APOE) gene.

According to the Mayo Clinic, APOE4 variants are known to increase the risk of Alzheimer’s disease and are associated with the development of more severe dementia.

On the other hand, APOE3 gene mutations so far do not appear to have any effect on Alzheimer’s disease risk.

But in 2019, researchers discovered that women from a Colombian family with two copies of a particular APO3 variant developed cognitive impairment 30 years later than expected.

Most people with the PAISA mutation develop mild cognitive impairment in their 40s, dementia in their 50s, and die from complications of dementia in their 60s.

But this woman, who carries the APO3 “Christchurch” variant, didn’t develop brain problems until she was in her late 70s.

In the new study, researchers dig into the medical history of a Colombian family to see if any other members may have benefited from the Christchurch variant.

The researchers analyzed nearly 1,100 descendants of the Colombian family and identified 27 additional individuals who carried the Paisa mutation as well as one copy of the Christchurch mutation.

All 27 family members had delayed onset of dementia or Alzheimer’s disease.

They began to show signs of cognitive impairment at an average age of 52, compared with 47 for family members who did not have the Christchurch variant. They also showed signs of dementia four years later than other relatives.

This is important because it shows it’s possible to prevent Alzheimer’s disease through the Christchurch variant, said Dr. Joseph Arboleda Velazquez, an associate scientist at Massachusetts Eye and Ear Infirmary and co-senior study author.

“The initial studies showed that prevention was possible, which was an important insight, but when you need two copies of a rare gene mutation, it’s really just a matter of luck,” Arboleda Velásquez says.

“Our new study is significant because it gives us greater confidence that this target is not only protective but also druggable,” Arboleda-Velásquez added. “We believe that therapeutics inspired by protected humans are likely to be more effective and safer.”

Brain scans and autopsies showed that patients with the Christchurch variant had healthier blood vessels, lower levels of the protein tau, and preserved activity in areas of the brain typically involved in Alzheimer’s disease.

The researchers concluded that further studies in larger, more ethnically diverse populations may shed more light on the protective effects of the Christchurch variant and determine whether it could be applied to the treatment of Alzheimer’s disease.

“As a next step, we are now focused on improving our understanding of brain resilience in the remaining family members who carry one copy of the Christchurch variant,” Quiroz said. “This involves conducting structural and functional MRI scans and cognitive assessments, as well as analysing blood samples to assess protein and biomarker profiles.”

Source: Massachusetts General Hospital Brigham, news release, June 19, 2024

By focusing on specific protective genetic mutations, researchers may be able to identify new ways to treat or prevent Alzheimer’s disease.