A man from a Colombian family with a history of Alzheimer’s disease helped scientists identify a mutation that protects against degenerative brain disease.
This unidentified patient, who had a high risk of developing Alzheimer’s disease based on his family history, had no symptoms until he was 67.
Imaging tests obtained when he was 73 years old revealed the presence of Alzheimer’s disease hallmarks like amyloid plaques and tau tangles in his brain, which led to the diagnosis of mild cognitive impairment at age 70. He had mild dementia before his death from pneumonia at age 74.
After his death, scientists were able to determine that he had a mutation in a gene responsible for controlling the production of reelin, a protein with critical roles in both standard and abnormal brain cell development.
In the man’s entorhinal cortex, which plays a crucial role in memory and learning, the mutation in reelin that improves reelin’s function appears to have decreased the number of tau tangles. This supports the hypothesis that the entorhinal area is a potential micro-target for dementia prevention.
The discovery of the reelin gene and its favored brain region should open a new front in the fight against Alzheimer’s, complementing current efforts to avoid amyloid beta protein plaques.
According to Arboleda-Velasquez, just 4–5% of research and development resources have been allocated to tau, while 95% have been spent on amyloid. This breakthrough comes from ongoing studies of a Colombian family of 6,000 people who inherit the “Paisa” mutation, a genetic variant that dramatically increases the risk of developing Alzheimer’s disease at a young age.
After 30 years of studying this family, scientists in 2019 finally identified the protective genetic mutation. The reelin mutation blocks phosphorylation, which triggers a structural change in naturally occurring tau proteins, preventing them from tangling with other tau filaments. Arboleda-Velasquez is optimistic that reelin might be used as a therapeutic to halt the progression of Alzheimer’s disease by blocking at least one pathway.
The most critical information is that patients should be given extra reelin because the mutation increases function.