Alzheimer’s disease is one of the most feared conditions of aging. It robs people of their memory, independence, and ability to think clearly.
Despite decades of research, there is still no cure.
More than six million Americans are living with Alzheimer’s today, and millions more are expected to be diagnosed in the coming decades.
For years, scientists have focused heavily on sticky clumps in the brain known as amyloid plaques. These gummy deposits of a protein called A-beta form between nerve cells and are considered a hallmark of the disease.
Because these plaques appear years before memory decline, many new drugs have been designed to remove them.
While some of these drugs can reduce plaque buildup, they have not dramatically improved symptoms, leaving researchers searching for new explanations and new treatment paths.
One promising avenue involves our genes. A team led by Stanford neurologist Dr. Mike Greicius has been studying the role of a gene called APOE. This gene comes in several versions, or variants, and which one you inherit can dramatically affect your risk of developing Alzheimer’s.
The APOE3 variant is the most common, and most people carry two copies of it—one from each parent. A second version, APOE2, is rare but appears to protect against Alzheimer’s.
Then there is APOE4, the variant that causes concern. Carrying one copy of APOE4 doubles or triples a person’s risk of Alzheimer’s compared to someone with two APOE3 copies.
Having two APOE4 copies raises the risk up to tenfold. About one in four people of European ancestry carry at least one copy of APOE4, and it shows up in more than half of Alzheimer’s patients from this group.
APOE4 also influences when symptoms begin. People with the variant typically develop memory loss five to ten years earlier than those without it.
But the story isn’t simple. The risk varies depending on ancestry and even sex.
For example, Japanese people with APOE4 face an especially high risk, while people of African descent who carry it are less affected.
Among women of European ancestry, carrying one copy of APOE4 significantly raises risk, whereas the effect in men is smaller.
Scientists have known since the 1990s that APOE4 is linked to Alzheimer’s, but exactly why has remained a mystery.
APOE makes a protein, ApoE, that shuttles fats and cholesterol through the body and brain. It may also play a role in immune defense. But until recently, it was unclear whether ApoE4 was simply weaker at doing its job—or whether it was actively harmful.
Greicius and his colleagues found a remarkable clue. In a large database of more than 56,000 people, they identified two older adults who had inherited a defective APOE4 gene that could not produce the ApoE4 protein at all. Both also carried one normal APOE3 gene. Despite being in their late seventies and nineties, neither showed signs of cognitive decline. In fact, their brains looked unusually healthy, with no buildup of amyloid plaque.
This discovery suggests that ApoE4 is not just underperforming—it may actually be toxic. People with APOE4 may be better off producing none of the protein than producing a normal amount. That flips the scientific debate and points drug development in a new direction. Instead of trying to boost ApoE4 activity, researchers may need to find ways to reduce it.
The challenge is that ApoE proteins do important work in the body, especially in controlling cholesterol. Completely shutting them down could cause serious problems. But Greicius believes it may be possible to lower ApoE4 levels safely without eliminating the protein altogether. The health of the two individuals in his study—who had one faulty APOE4 copy and one normal APOE3 copy—suggests that reducing ApoE4 could protect the brain without damaging the heart or other organs.
The findings also highlight how genetics can shape not only the risk of Alzheimer’s but also the best treatment approach. A drug that works for someone with APOE3 might not work for someone with APOE4. Personalized medicine, where therapies are tailored to a person’s genetic profile, may be the future of Alzheimer’s care.
For now, there is no simple way to avoid APOE4. It is part of the genetic lottery. But by understanding how it works and why it raises risk, scientists hope to develop treatments that can neutralize its harmful effects. As Dr. Greicius puts it: “ApoE4 is not a wimp. It’s a cutthroat. Get rid of it.”
This new line of research offers a ray of hope in the long fight against Alzheimer’s. It suggests that by targeting one of the disease’s strongest genetic risk factors, doctors may one day slow or even prevent its devastating effects.
If you care about Alzheimer’s, please read studies about the likely cause of Alzheimer’s disease , and new non-drug treatment that could help prevent Alzheimer’s.
For more health information, please see recent studies about diet that may help prevent Alzheimer’s, and results showing some dementia cases could be prevented by changing these 12 things.
Source: Stanford University.
