This one gene may explain most Alzheimer’s cases

 A new analysis led by researchers at University College London suggests that Alzheimer's disease may depend far more on one gene than previously recognized. The study estimates that more than 90% of Alzheimer's cases might not develop without the influence of a single gene called APOE.

The researchers also found that the gene's impact extends beyond Alzheimer's alone. Their analysis indicates that nearly half of all dementia cases may also rely on APOE's contribution.Published in npj Dementia, the findings point to APOE and the protein it produces as a major yet often overlooked target for drug development. Targeting this gene could open the door to preventing or treating a large share of dementia cases worldwide.

Understanding the APOE Gene and Its Variants

Scientists have known for decades that APOE is linked to Alzheimer's disease. The gene comes in three common forms, or alleles, called ε2, ε3, and ε4. Each person carries two copies of the gene, which results in six possible combinations* of these variants.

Research dating back to the 1990s showed that people who carry one or two copies of the ε4 variant face a much higher risk of developing Alzheimer's compared with those who inherit two ε3 copies. By contrast, people with ε2 generally have a lower risk than ε3 carriers.

Why Scientists Say APOE's Role Has Been Underestimated

Lead author Dr. Dylan Williams (UCL Division of Psychiatry and Unit for Lifelong Health and Ageing at UCL) said: "We have long underestimated how much the APOE gene contributes to the burden of Alzheimer's disease. The ε4 variant of APOE is well recognized as harmful by dementia researchers, but much disease would not occur without the additional impact of the common ε3 allele, which has been typically misperceived as neutral in terms of Alzheimer's risk.

"When we consider the contributions of ε3 and ε4, we can see that APOE potentially has a role in almost all Alzheimer's disease. Consequently, if we knew how to reduce the risk that the ε3 and ε4 variants confer to people, we may be able prevent most disease from occurring."

The Largest Modeling Study of APOE's Population Impact

This research represents the most comprehensive modeling effort so far to estimate how many Alzheimer's and dementia cases across the population are tied to common APOE variants. The team combined evidence linking ε3 and ε4 to Alzheimer's, broader dementia diagnoses, and the brain changes that precede the disease.

Source: ScienceDaily