Genetic research in relation to Alzheimer’s disease became a topic of conversation in 1993 when Dr. Judes Poirier led a research team to study how the APOE gene may influence a person’s risk for Alzheimer’s disease. The published journal article that shared the results from this study is the first one on our list of 5 Research Articles About APOE. Since 1993, scientists have continued genetic-related research studies to explore this topic. The articles on our list span the past 20 years. They are listed in chronological order, with Dr. Poirer’s 1993 article as the first and an article from 2022 as the last.
Numerous research articles have been published on APOE and Alzheimer’s disease. Here are five genetic research studies on this topic that we found interesting:
1. APOE in 1993
Apolipoprotein E Polymorphism and Alzheimer’s Disease, written by Dr. Judes Poirier and colleagues, was published in 1993.
The study was completed with 91 people diagnosed with Alzheimer’s and 74 people without Alzheimer’s. Blood samples were used to determine their specific alleles for the APOE gene. Results showed that Alzheimer’s patients often had a copy of the APOE-ε4 allele. This led to the conclusion that when a person has an APOE-ε4 allele they may be at a higher risk for Alzheimer’s disease than someone with an APOE-ε2 or APOE-ε3 allele.
2. APOE and Cognitive Decline in Active Professional Football Players
Lower Cognitive Performance of Older Football Players Possessing Apolipoprotein E ε4, written by Dr. Kenneth Kutner and colleagues, was published in 2000.
As the title suggests, the research team was trying to find the relationship between APOE alleles and cognitive decline in football players. There were 53 active American professional football players who participated in the study by providing a saliva sample and doing cognitive assessments. 14 of the players had one copy of the APOE-ε4 allele. Players were both younger with low exposure to contact (head injury; concussion) and older with high exposure to contact. Results showed that APOE-ε4 carriers with high exposure scored lower on the cognitive assessments than the other participants. The authors gather that APOE status may affect the ability of the brain to heal after a football contact-related injury. Further research is needed to explore this idea.
3. APOE Alleles
Apolipoprotein E and Alzheimer Disease: Risk, Mechanisms and Therapy, written by Dr. Liu Chia-Chen and colleagues, was published in 2013.
This article takes a deeper dive into how an APOE protein will act in the body, depending on the alleles responsible for creating it. The most common alleles of the APOE gene are ε2, ε3, and ε4. The authors review current information known about the way various combinations of these alleles affect the central nervous system. This information is then linked to Alzheimer’s disease and other dementias to give a clearer picture of how APOE affects risk for these diseases through the impact on the protein it is responsible for creating.
4. APOE and Diet
Genotype Patterns at CLU, CR1, PICALM and APOE, Cognition and Mediterranean Diet: The PREDIMED-NAVARRA Trial, written by Dr. Elena Martinez-Lapiscina, was published in 2014.
This research group explored the relationship between diet and cognitive decline. A total of 522 participants were enrolled in the PREDIMED-NAVARRA study, and they followed a traditional Mediterranean diet (MedDiet) or a low-fat diet. The MedDiet consists of olive oil as the main fat, lots of plant-based foods, moderate amounts of fish and dairy products, and low amounts of meat. The authors were interested in the diet’s ability to improve cognition and if a person’s genes would have an impact. Due to the low number of APOE-ε4 carriers in the study, the authors couldn’t determine if the gene impacted the effects of diet on cognition. However, this article also explores genes other than APOE. CLU, CR1, and PICALM genotypes were also studied. This allowed the research team to look at individual gene influence and genetic profile (combination of various forms of genes) impact.
For example, results showed that after following the MedDiet, participants with at least one copy of the CLU-rs11136000 gene variant, also known as the T allele, improved their scores on a cognitive assessment that examined orientation, verbal recall, language, and visual construction.
Similarly, results showed that after following the MedDiet, participants with a genetic profile consisting of the CR1-rs3818361, CLU-rs11136000, and PICALM- rs3851179 genes, significantly improved their scores on a cognitive assessment that observed executive function and visuospatial skills.
5. APOE and Obesity
5. Reduced Brain Activity During a Working Memory Task in Middle-Aged Apolipoprotein E ε4 Carriers with Overweight/Obesity, written by Dr. Jermon Drake and colleagues, was published in 2022.
This article summarizes a study of 48 adults who completed a working memory task during an MRI scan. A working memory task is a type of cognitive assessment that measures short-term memory. For example, this study used a task setup to ask participants if the letter presented on the screen is the same as the letter shown before that letter or the letter before that. This research study observed how the brain activates during the task. Results concluded that obesity and the APOE-ε4 allele are both risk factors for cognitive decline.
What Will be Published Next?
Researchers continue to explore interventions and therapies that might be more beneficial for individuals with a genetic risk for Alzheimer’s disease. For example, the Physical Activity and Alzheimer’s Disease 2 (PAAD2) study, led by Dr. Jenny Etnier, is underway and will be joining the body of literature found on the important topic of APOE and Alzheimer’s disease. If you want to learn more about how PAAD2 is contributing to answering questions about Alzheimer’s disease, click here.