The genetic link to Alzheimer’s is well-known in the scientific community. New research suggests one of the risk-related genes begins to do damage to the brain 50 years before Alzheimer’s is seen.
Paul Thompson , a UCLA professor, reports his work in the current online edition of the Journal of Neuroscience. Thompson and his colleagues report that a particular form of the CLU gene impairs the development of myelin, the protective covering around the neuron’s axons in the brain, making it weaker and more vulnerable to the onset of Alzheimer’s much later in life.
The research team scanned the brains of 398 healthy adults ranging in age from 20 to 30 using a high-magnetic-field diffusion scan (called a 4-Tesla DTI), a newer type of MRI that maps the brain’s connections. They compared those carrying a C-allele variant of the CLU gene with those who had a different variant, the CLU T-allele.
They found that carriers of the CLU-C gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing the disease later in life. The discovery of what this gene does is interesting on several levels, said Thompson, the senior author of the study.
“For example, Alzheimer’s has traditionally been considered a disease marked by neuronal cell loss and widespread gray-matter atrophy,” he said.
“But degeneration of myelin in white-matter fiber pathways is more and more being considered a key disease component and another possible pathway to the disease, and this discovery supports that.”
Thompson said four things are surprising with the discovery of this gene’s function:
- 1. This risk gene damages the brain a full 50 years before people normally get Alzheimer’s. The damage can be seen on an MRI scan, but there are no symptoms yet.
- 2. It’s now known what this mysterious gene does — namely, make your brain wiring vulnerable to attack by impairing the wiring before any senile plaques or tangles develop.
- 3. Rather than being a gene that few people have, a whopping 88 percent of Caucasians have it. “So I guess you could say the other 12 percent have an ‘Alzheimer’s resistance gene’ that protects their brain wiring,” said Thompson.
- 4. Finally, he said, knowing the role of this gene is useful in predicting a person’s risk of the disease and in seeing if you can step in and protect the brain in the 50-year time window before the disease begins to develop.
Of course, the obvious question is if most of us have this “bad” gene, why isn’t Alzheimer’s rampant in young people?
Less myelination in CLU-C carriers may not translate into poorer cognition in youth, said Thompson, because the brain can compensate. “The brain has a lot of built-in redundancy — miles and miles of brain connections,” he said.
Still, he said, with the passage of time — and when exacerbated by other factors, such as normal neuron death as we age and plaque and tangle development in the early stages of Alzheimer’s — reduced myelin integrity could contribute to cognitive impairment.
“So it’s unlikely we are seeing the earliest possible signs of Alzheimer’s-associated brain changes in these young people,” Thompson said. “It’s more likely the reduced fiber integrity represents an early developmental vulnerability that may reduce brain resilience to later Alzheimer’s disease pathology.”
Knowing that an individual is at a genetic risk for Alzheimer’s is important for evaluating treatment and prevention strategies.
“We know that many lifestyle factors, such as regular exercise and a healthful diet, may reduce the risk of cognitive decline, particularly in those genetically at risk for Alzheimer’s, so this reminds us how important that is,” he said.