Research led by Niigata University suggests that the Alzheimer’s disease risk associated with carriage of the APOE4 gene variant is not as high in Japanese populations as earlier studies reported.
A study published in 1997 suggested that Japanese people who carried two APOE4 alleles had a more than 30-fold increased risk for developing Alzheimer’s disease compared with people with two copies of the more common APOE3 allele.
Writing in the journal Molecular Neurodegeneration, co-lead author Takeshi Ikeuchi, MD, PhD, a professor at Niigata University, and colleagues challenge this earlier statistic. Results from a new meta-analysis carried out by Ikeuchi and team suggest that Japanese APOE4 homozygotes are actually at approximately 12-15-fold increased risk of developing Alzheimer’s compared to those carrying two copies of APOE3.
APOE (apolipoprotein E) is a protein that transports lipids in the blood and brain and helps with neuronal repair after injury. The E4 variant increases Alzheimer’s risk because it alters the way lipids are processed and is associated with greater amyloid‑beta and tau accumulation, more neuroinflammation, and earlier onset of disease symptoms compared with other variants.
Depending on the population, the most common APOE gene variant is E3, which has an average global frequency of around 80%, followed by E4 at around 13% and then E2 at around 7%. While E4 is known to increase the risk for Alzheimer’s disease, E2 is protective in those who carry it with one copy linked to an approximate halving of Alzheimer’s risk and two copies can reduce risks by as much as 85% compared with having two copies of E3.
In European populations, about whom the most genetic information is available, carriage of two copies of the APOE4 allele is linked to an approximate 10-15-fold increase in Alzheimer’s risk. However, this is not the case in all populations. East Asian populations were previously thought to be at higher risk, linked to the earlier Japanese study and also higher estimates in Korean populations. But African or African American populations are thought to have a lower risk linked to being an APOE4 homozygote with an estimated 5-7 fold higher risk than a APOE3 homozygote.
For the current meta-analysis, Ikeuchi and colleagues included 21 Japanese case–control studies that spanned from the early 1990s to the 2010s and reported APOE genotypes in Alzheimer’s patients and controls.
They found that being an APOE4 homozygote substantially increased Alzheimer’s risk in Japanese people, but less than previously thought. Pooled risk increases for E4/E4 vs E3/E3 were 15.5 for early‑onset, 12.5 for late‑onset, and 13.5 for all Alzheimer’s disease, indicating about a 12–15‑fold risk increase for people carrying two copies of APOE4 overall.
Earlier meta-analyses had reported risk increases of 21.8–33.1, so this study revises the Japanese E4 homozygote effect downward to a figure similar to that seen in European populations.
“Accurate risk estimates are essential for both research and clinical practice,” said Ikeuchi in a press statement. “As the field moves toward earlier diagnosis and prevention of Alzheimer’s disease, reliable genetic risk information will become increasingly important.”
The post <i>APOE4</i>-Linked Alzheimer’s Risk Lower Than Estimated in Japanese People appeared first on Inside Precision Medicine.