“Groundbreaking Discovery: Protective Mutation Found in Colombian Family Could Hold Key to Dementia Treatment”

Today, approximately 6,000 of his descendants live in the Colombian region of Antioquia in the Andes.

1200 of them have the mutation known as ‘Paisa’ or ‘E280A’. The genetic mystery behind the high rate of early-onset Alzheimer’s has puzzled researchers around the world for years.

Now an international research team has made a potentially groundbreaking discovery that could hold the key to a treatment for dementia.

A man in the family was a carrier of the mutation, but did not develop Alzheimer’s until he was 72 years old – decades later than expected.

After his death, his brain was examined and a surprising genetic mutation was discovered, which seems to have protected the man against Alzheimer’s for years.

This is the conclusion of an international study published in Nature Medicine.

Mutation makes resilient

In the vast majority of patients with Alzheimer’s disease, the beta-amyloid protein accumulates over time and clumps into plaques in the brain.

At the same time, another protein called tau accumulates in tangled networks called fiber tangles.

The examination of the Colombian man’s brain did indeed show the characteristic clumps of beta-amyloid, but hardly any tau clumps were found in the brain region usually affected first in Alzheimer’s disease, the entorhinal cortex.

The explanation, the researchers say, is that the man had a different mutation, which they named COLBOS — an abbreviation for Columbia and Boston, where most of the study’s authors are from. This mutation made him resistant to dementia.

The researchers know of only one previous example of a person with the Paisa mutation who did not develop Alzheimer’s at a young age.

That was a Colombian woman, who died in 2020 at the age of 77. According to the researchers, she had another protective mutation that kept the disease at bay for a long time.

With this new knowledge, the researchers hope to eventually be able to develop molecules that mimic the effect of the protective mutations.

Another possibility is to use gene therapy to modify the DNA in the brain to mimic the effect of the mutations that appear to prevent dementia.