Initially recognized for its role in cardiovascular disease, the APOE gene also plays a role in Alzheimer's disease (AD). The protein produced by this gene transports fats (lipids) and cholesterol in the body. However, APOE has several common variants (or "alleles") whose effects vary. The e4 allele, in particular, is the most prevalent genetic factor associated with late-onset Alzheimer's disease and causes an increased risk and/or earlier onset. Its impact varies depending on whether the mutation appears on one or both chromosomes, and on a person's race and ethnicity (i.e., risk is not increased uniformly across all ethnic groups). Scientists are still trying to find out the reasons why. Some clues may lie with ApoE4 interactions with the immune system, where it influences inflammation and a type of cellular damage known as oxidation. Also, whereas ApoE helps break down amyloid-beta protein located in and around neurons, the ApoE4 version is less effective at doing so.
Explore More of Our 360° Research Approach
- Tangling with Tau
- Battling Amyloid Beta
- Blood and the Brain in Dementia
- Immunity and Inflammation
- Cell Death
- New Approaches
Genes are the “master blueprint” that instructs our cells to make unique proteins which in turn build, operate, and repair human tissue. Humans have an estimated 24,000 genes along our 23 matched pairs of chromosomes (46 in all), and “genomics” refers to the field that studies all of them at once.
A biological marker (biomarker) is a measurable substance in an organism whose presence is indicative of some phenomenon such as disease or infection. Biomarkers can help doctors and scientists diagnose diseases and health conditions, find health risks in a person, monitor responses to treatment, and see how a person's disease or health condition changes over time.
Tangling with Tau
Tau is a small protein with a short name but a large reputation because of its association with multiple brain diseases, including Alzheimer’s disease (AD). The tau protein is predominantly found in brain cells (neurons).
Battling Amyloid Beta
There are many versions of amyloid protein in the human body, and most serve a useful role. One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of amyloid plaques (abnormally configured proteins) between nerve cells (neurons) in the brain.
Blood and the Brain in Dementia
Scientists are interested in developing a screening tool for Alzheimer’s disease (AD) in blood. A simple blood draw is much less invasive than a spinal tap and may prove more cost-effective. Developing blood biomarkers that accurately depict brain changes have proven challenging, as levels of AD hallmark proteins in the blood are low, but there are some very recent promising results observing tau and the ratio of Aβ42 and Aβ40.
Immunity and Inflammation
One theory about Alzheimer’s disease (AD) is that it may be triggered, in part, by a breakdown in the brain’s immune system.
The human brain has an estimated 100 billion neurons. Extending from each of them is a long fiber, known as an “axon,” which can run several feet. Each axon forms a connection, known as a “synapse” with another neuron, creating a circuit over which brain signals travel. In Alzheimer’s disease (AD), individual neurons die and do not regenerate; while others have brains that are more are resilient and respond to meet changing demands.
Years of innovative and dedicated research have paid off with the discovery of numerous factors contributing to Alzheimer’s disease (AD) pathology. With a disease as complex as this one, it’s very helpful to find multiple points where it may be possible to slow or halt its progress.