New analysis lowers Alzheimer’s risk estimate for Japanese APOE-e4 homozygotes
Niigata University researchers say Japanese people with two APOE-e4 copies face high Alzheimer’s risk, but less than older estimates suggested.
By Tom Brennan · Health & Medicine Correspondent
3 min read
Japanese people who inherit two copies of the APOE-e4 variant may face a lower Alzheimer’s disease risk than a widely cited 1990s estimate suggested, according to Niigata University researchers. The finding matters for genetic risk assessment as Alzheimer’s research increasingly focuses on earlier diagnosis and prevention.
The team reported its analysis in Molecular Neurodegeneration, where it reexamined evidence on APOE-e4 homozygosity, known as e4*4, in the Japanese population. Niigata University described the work as the first broad reassessment of that risk in nearly 30 years.
Alzheimer’s disease is the most common cause of dementia worldwide, according to Niigata University. The APOE gene is regarded as the strongest genetic risk factor for late-onset Alzheimer’s, and people with two copies of the APOE-e4 variant have been known to carry a high risk of developing the disease.
A 1997 international meta-analysis estimated that Japanese people with the e4*4 genotype had more than 30 times the Alzheimer’s risk of people with the common e3*3 genotype, according to the researchers. That figure has been cited in scientific literature for decades, Niigata University said.
Since that earlier analysis, researchers in Japan have published many additional case-control studies. To update the estimate, the Niigata University team reviewed and combined data from 21 Japanese case-control studies.
The new meta-analysis found that e4*4 was associated with an approximately 12- to 15-fold increase in Alzheimer’s disease risk. The researchers said that remains one of the strongest known genetic risk factors for the disease, but it is below the more than 20- to 30-fold risk estimates that have circulated in the field.
Akinori Miyashita, an associate professor at Niigata University and an author of the study, said the genotype remains a strong risk factor in Japanese populations. He said the updated evidence indicates the risk is less extreme than earlier work suggested and offers a more current estimate based on research accumulated over three decades.
The study also found that the Japanese estimate is broadly similar to results from large studies of people with European ancestry, according to Niigata University. The researchers said evidence from Chinese populations also shows comparable effect sizes, suggesting the impact of e4*4 may be more consistent across populations than earlier assumptions implied.
Takeshi Ikeuchi, a professor at Niigata University and an author of the study, said accurate risk estimates are needed for both research and clinical practice. He said reliable genetic risk information will become more useful as Alzheimer’s work shifts toward earlier detection and prevention.
The researchers said their results can serve as an updated basis for genetic risk assessment and future prevention studies. They also cautioned that carrying APOE-e4 does not mean a person will develop Alzheimer’s disease, because environmental and lifestyle factors also contribute to risk.
The publication is titled “A reappraisal of APOE genetic effects on Alzheimer’s disease risk in the Japanese population: a meta-analysis” and appeared in Molecular Neurodegeneration. The listed authors include Akinori Miyashita and colleagues.
This story draws on original reporting from Medical Xpress.