Scientists identify gene behind partial brain vulnerability to Alzheimer’s disease

While everyone carries some version of the APOE gene, those who carry the APOE4 variant are up to 12 times more likely to develop Alzheimer’s disease than the general population. Images for representation. | | Photo credit: Getty Images

Scientists have uncovered why certain parts of the brain are particularly vulnerable to Alzheimer’s damage. It comes down to the APOE gene, the greatest genetic risk factor for the disease.

The parts of the brain where APOE is most active are the areas most vulnerable to damage, according to researchers at the University of Washington.

Everyone carries some version of the APOE gene, but people with the APOE4 variant are up to 12 times more likely to develop Alzheimer’s than the general population and at a younger age, they said. .

Research results published in journals Science Translational Medicinea well-researched Alzheimer’s disease that helps explain why Alzheimer’s symptoms change from time to time and suggests that as-yet undiscovered biological mechanisms may play an important role in this disease. I have emphasized the aspects that are not.

A typical pattern of worsening brain tissue damage often begins with memory loss, followed by confusion and difficulty thinking. Toxic clusters of proteins first focus on memory areas before spreading to parts of the brain important for thinking and planning.

But Brian A. Gordon, the study’s lead author, says there are some rare, atypical forms of Alzheimer’s that first develop language and vision problems rather than memory problems. increase.

“When we scan their brains, we see damage in language or visual areas, but not in memory areas. People with atypical Alzheimer’s are easier to study in groups where everyone has the same set, so research are often excluded from the symptoms.

“But this heterogeneity tells us that there are things we still don’t understand about how and why Alzheimer’s disease develops the way it does. “There’s a reason other areas aren’t damaged, and we don’t know yet,” Gordon said.

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Alzheimer’s disease starts with a brain protein known as amyloid beta. Protein begins to build up in plaque over 20 years before people show the first signs of neurological problems.

After years of accumulation of amyloid, tangles of another brain protein, tau, begin to form. Soon after, the affected tissue begins to wither and die, and cognitive decline begins.

To understand why Alzheimer’s brain damage occurs, Gordon and colleagues surveyed 350 volunteers for the Memory and Aging Study through the Charles F. and Joanne Knight Center for Alzheimer’s Disease Research in the School of Medicine.

Participants underwent brain scans, allowing researchers to measure the amount and location of amyloid plaques and tau tangles, as well as the volume of various brain regions.

The researchers compared the patterns of protein mass and tissue damage in the volunteers to the gene expression patterns of APOE and other genes associated with Alzheimer’s disease depicted in the Allen Human Brain Atlas. Allen Institute for Brain Science.

“There was a close match between where we saw high APOE expression and where we saw tau tangles and tissue damage,” Gordon said.

“It’s not just APOE. If you look at the top 20 genes associated with Alzheimer’s disease, for example, they’re all expressed in a similar pattern in the temporal lobe. There’s something fundamentally different about these regions.” , are more susceptible to brain damage in Alzheimer’s disease, and the differences are likely hardwired from birth and influenced by human genetics.”

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Alzheimer’s researchers have long known that APOE4 increases the accumulation of amyloid-beta in people’s brains. David Holtzman and colleagues studied mice that develop tau tangles but not amyloid plaques and show that APOE4 also increases tau-induced damage, even in the absence of amyloid.

To assess the impact of high-risk variants of APOE on tau-associated brain injury in humans, researchers classified each participant into whether they carried a high-risk variant and identified protein clusters and atrophy in the brain. was analyzed.

“APOE4 carriers are more likely to start accumulating amyloid, putting them on the road to Alzheimer’s disease,” Gordon said. , which leads to more atrophy, which is a double blow to the brain.” Atrophy refers to weakening or degeneration, especially due to lack of use.

In future studies, Gordon and colleagues will investigate how patterns of gene expression are associated with patterns of tau damage in patients with atypical Alzheimer’s disease.

“When we look at people who have vision problems, are there specific genetic signatures that correspond to damaged areas of the brain? We wonder why some people have these altered patterns.” “I want to know what that means for how Alzheimer’s disease develops, and how it can be treated,” Gordon said.