New Insights into Alzheimer’s Therapies

Researchers are suggesting that new treatments for Alzheimer’s disease should focus on a specific gene associated with the condition. They believe that if the harmful effects of this gene could be neutralized, many cases of the disease might not occur at all.

This appeal comes after the introduction of the first drugs designed to treat Alzheimer’s by removing toxic proteins from the brain. Although these drugs have shown some effectiveness in slowing the progression of the disease, the benefits are limited, and they have been rejected for general use by the UK’s National Institute for Health and Care Excellence.

In their search for alternative treatments, scientists from UCL are urging drug developers to concentrate on two concerning variants of a gene known as Apoe. They assert that therapies targeting these variants hold “vast potential” for preventing Alzheimer’s disease.

Dr. Dylan Williams, a genetic epidemiologist at UCL, emphasized, “A significant portion of Alzheimer’s cases wouldn’t occur without this single gene: Apoe. We should view it as a direct target for intervention. Almost all potential Alzheimer’s cases could benefit from addressing Apoe-related issues.”

Currently, over half a million individuals in the UK and more than 40 million globally are coping with Alzheimer’s, which is the most prevalent form of dementia. Various genes contribute to the risk of developing Alzheimer’s, but lifestyle choices also play a crucial role—factors like smoking, obesity, diabetes, high blood pressure, and cholesterol levels can all increase risk.

Williams and his team analyzed medical data from over 450,000 participants of European descent to determine how different variants of the Apoe gene contribute to the incidence of Alzheimer’s. Each person inherits two copies of the gene—one from each parent—and there are three primary variants: Apoe2, 3, and 4.

It’s well-known that individuals with two copies of the Apoe4 variant are at high risk for Alzheimer’s. However, interestingly, 40% to 70% of them don’t actually develop the disease. The Apoe3 variant is generally viewed as neutral while the Apoe2 variant is seen as protective.

But Williams suggests a different perspective. He argues that compared to having two copies of Apoe2, both Apoe3 and Apoe4 increase the likelihood of developing Alzheimer’s. In a paper published in the journal npj Dementia, the team estimates that eliminating these variants could prevent 72% to 93% of Alzheimer’s cases, along with about 45% of all dementia cases. “If we could negate the harmful impacts of Apoe3 and 4, we could potentially prevent a significant portion of Alzheimer’s,” they conclude.

That’s a big “if.” The Apoe gene plays a key role in moving cholesterol and fats throughout the body and brain, so completely eliminating it could lead to other issues. Future treatments could aim to edit the gene variants or reduce their activity, but those options are still far from reality and certainly carry risks.

Moreover, a huge majority of individuals—over 99% in the study—carry either Apoe3 or Apoe4. Consequently, preventing Alzheimer’s might involve treating almost the entire population, possibly through invasive gene editing techniques.

The study has elicited mixed reactions. Tim Frayling, a professor of human genetics at the University of Geneva, noted that claiming over 90% of Alzheimer’s cases wouldn’t exist without the Apoe gene is akin to saying that most road traffic deaths wouldn’t occur without cars. He emphasizes that people shouldn’t be overly concerned about carrying the risk versions of the gene since almost everyone does.

In contrast, Tara Spires-Jones, a professor of neurodegeneration at the University of Edinburgh, points out that grasping the risk factors that can leave the brain susceptible to Alzheimer’s is crucial for developing effective prevention and treatment strategies. She reinforces that Apoe is one of the most significant genetic risk factors.

Dr. Sheona Scales from Alzheimer’s Research UK added that while evidence around Apoe3’s contribution to Alzheimer’s risk is considerable, it’s essential to remember that not everyone with these gene variations will develop dementia—other factors play a part as well.

This research opens up numerous questions, such as how Apoe3 and Apoe4 may contribute to Alzheimer’s risk, how these effects might differ in people of non-European descent, and whether targeting these variants could lead to promising treatment and prevention routes. However, due to the complexity of Alzheimer’s risk, Apoe testing isn’t available through the NHS for those concerned about their risk of developing the disease. If there are concerns regarding dementia risk, consulting with a GP is advisable.