Researchers studying a large Columbian family with hereditary Alzheimer's disease have discovered a protective mutation in the RELN gene called Reelin-COLBOS that may provide new insights into how Alzheimer's disease develops. The study, which examined 1,200 people with genetic testing, brain imaging, and examination of brain tissues after death, found that a man carrying a genetic mutation known to cause early-onset Alzheimer's disease postponed development of dementia until age 72. The man also carried the newly discovered Reelin-COLBOS mutation, which appears to provide protection from Alzheimer's disease. His sister, with the same hereditary risk, was found to have a mutation in a different protective gene that allowed her to avoid cognitive decline until age 58 and dementia until 61.
The protective Reelin-COLBOS mutation plugs into a receptor in the cells of the brain, diminishing the activation of a protein called tau, known to form tangles in brains with Alzheimer's disease. Imaging of the man's brain showed that although he had a lot of amyloid plaques, he had very few tau tangles in a region of his brain called the entorhinal cortex. If a mutation in another gene, called APOE, plugs into that receptor instead, it increases tau activation, speeding up the development of those tangles and cognitive decline.
This new genetic information may change the way researchers think about and develop treatments for Alzheimer's disease. Finding, understanding, replicating, and mimicking the actions of protective mutations may be key to creating more precision medicines and fending off the onset of Alzheimer's and other diseases. This approach has already been successful in other areas of medicine. For example, researchers studied a woman with very low cholesterol who was found to carry genetic mutations from both parents that caused her astonishing LDL cholesterol level of 14. They used that information to create a medication to treat patients with very high cholesterol. The same may someday be true for Alzheimer's.