Researchers at Niigata University have conducted the first comprehensive reassessment of risks associated with Alzheimer’s disease (AD) in nearly 30 years. APOE-e4 Homozygous (e4*4) among the population of Japan. Their findings suggest that the risks, while still large, are lower than estimates that have been widely cited since the 1990s.
Alzheimer’s disease is the most common cause of dementia worldwide. Among the many factors that influence disease risk, Apoe Genes are thought to be the strongest genetic risk factor for late-onset Alzheimer’s disease. Individuals who inherit two copies APOE-e4 Variants are known to have a particularly high risk of developing the disease.
In 1997, a groundbreaking international meta-analysis revealed that the Japanese e4*4 had more than 30 times higher risk of Alzheimer’s disease compared to people with the most common form of Alzheimer’s disease Apoe genotype, e3*3 (Farrer LA, others. JAMA (1997)). This estimate has been cited repeatedly in the scientific literature for nearly 30 years. However, since then, many more case-control studies have been published in Japan, increasing the need for more evidence-based and up-to-date evaluations.
To address this question, the research team systematically reviewed and synthesized data from 21 case-control studies in Japan. By integrating the available evidence, they found that: e4*4 It is associated with an approximately 12- to 15-fold increase in AD risk. Although this still represents one of the strongest known genetic risk factors for the disease, it is significantly lower than long-standing estimates of >20-30 times (Farrer LA, others. JAMA (1997); Bertram L. others. Nat Genet (2007)).
” e4*4 “The genetic risk factors for Alzheimer’s disease in Japanese people remain very strong,” explains Dr. Akinori Miyashita, associate professor at Niigata University. By incorporating evidence accumulated over the past 30 years, we were able to provide more robust and up-to-date estimates. ”
The study also showed that the risks observed in the Japanese population were similar to estimates reported in large studies of people of European ancestry (Farrer LA, others. JAMA (1997); Bertram L. others. Nat Genet (2007); Belloy I, others. JAMA Neurol (2023)). This finding, along with evidence from a Chinese population showing comparable effect sizes (Liu M, others. Sci Rep (2014)), the following effects have been suggested. e4*4 It may be more consistent across populations than previously thought.
Accurate risk estimation is essential for both research and clinical practice. As the field moves toward early diagnosis and prevention of Alzheimer’s disease, reliable genetic risk information will become increasingly important. ”
Mr. Tsuyoshi Ikeuchi (Professor, Niigata University)
The researchers believe their findings provide a modern foundation for future research aimed at genetic risk assessment and disease prevention. They also APOE-e4 The variant does not guarantee that a person will develop Alzheimer’s disease, as many environmental and lifestyle factors also contribute to disease risk.
This study highlights the importance of regularly reevaluating long-standing scientific assumptions as new evidence accumulates and demonstrates how modern analyzes can improve understanding of disease risk in diverse populations.
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Reference magazines:
Miyashita, A., others. (2026) Reassessing the genetic influence of APOE on Alzheimer’s disease risk in Japanese: a meta-analysis. molecular neurodegeneration. DOI: 10.1186/s13024-026-00963-z. https://link.springer.com/article/10.1186/s13024-026-00963-z.
