Another Key Gene Discovered for Alzheimer’s Disease

The consensus among scientists has been that the Apolipoprotein E (ApoE4) gene is the main marker of Alzheimer's disease and many other dementias, but a new study has added another key player into the mix.

The ApoE gene is instrumental in forming lipoproteins, which are molecules that carry cholesterol and other fats through our bloodstream. ApoE has several slightly different versions, and one of them, called e4, has been strongly associated with the risk of developing Alzheimer's disease. Moreover, the ApoE4 gene is linked to the buildup of amyloid plaque, which is a clumpy protein found in the brain tissue of Alzheimer's patients.


A group of international scientists led by those at the University of Southern California (Los Angeles, CA, USA) interviewed participants once every two years between 1996 and 2012, and another group did so between 2002 and 2012. For the test of immediate recall, the participants were read a list of 10 nouns and were asked to say them back to the interviewer immediately. But for the delayed recall test, the interviewer waited five minutes before asking participants to repeat the list.

The team adjusted the data for age and sex also examined the genetic data from 7,486 American participants and 6,898 European participants. In 2006, the first wave was collected from buccal swabs using the Qiagen Autopure method. In 2008, the second wave was collected using Oragene saliva kits and extraction method. Both waves were genotyped using the HumanOmni2.5-4v1 array.

Overall, the scientists examined 1.2 million genetic variations in the human genome, looking for associations between these gene variations and the results of the memory tests. Only the Translocase of Outer Mitochondrial Membrane 40 (TOMM40) gene was found to be strongly associated with a decline in immediate and delayed recall. The results also showed an association with the "traditional" genetic culprit, ApoE4, but the link was not as strong. Additionally, the analysis revealed that the e3 variant of the ApoE gene was also associated with a low memory score, when found in conjunction with the TOMM40 gene.

Carol A. Prescott, PhD, a professor of Psychology and senior author of the study said, “Our findings indicate that TOMM40 plays a larger role, specifically, in the decline of verbal learning after age 60. Other studies may not have detected the effects of TOMM40. The results from this study provide more evidence that the causes of memory decline are even more complicated than we thought before, and they raise the question of how many findings in other studies have been attributed to ApoE4 that may be due to TOMM40 or a combination of TOMM40 and ApoE4.” The study was published on August 11, 2017, in the journal Public Library of Science ONE.

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