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How the APOE gene affects the risk of developing Alzheimer’s Disease

There are four types of the apolipoprotein E (APOE) gene.  Everyone receives one copy of the APOE gene from their mother and one from their father.  The type of APOE genes inherited plays a large role in determining the risk of developing late-onset Alzheimer’s disease (AD). APOE 4 confers an increased risk and APOE 2 reduces the risk of developing AD. Because every person has two copies of the APOE gene, they can sometimes inherit one copy of APOE4 and sometimes inherit two copies of APOE4.  Inheriting two copies of APOE4 confers an even greater risk of developing AD than inheriting one copy.

One of the hallmarks of AD is the deposition of a protein called amyloid into the brain.  APOE4 is thought to increase the risk of developing AD by promoting earlier and greater deposition and clumping of amyloid in the brains of APOE4 carriers. Additionally, APOE4 affects the protein tau which causes neurodegeneration and certain immune responses (microglial) in the brain. Finally, the APOE4 genotype is less efficient than the other types of APOE genes.  The gene is involved in various functions in the brain, including lipid transport, the well-being and plasticity of synapses (the junctions between nerve cells through which the nerve cells communicate), glucose metabolism, and cerebrovascular function.

The advances in understanding how the APOE gene impacts the risk of developing AD affords great promise for the treatment and prevention of this devastating disorder as it provides a target for new therapies.


The BeCareLink Neuro App has cognitive assessments and other quantitative measures of neurologic function that can help detect AD earlier, allowing for earlier intervention, and can act as a monitoring tool, helping clinicians to detect changes sooner.  Further, the children of AD victims worry that they may be developing dementia.  Using the BeCare Neuro App for screening can give relief or signal it’s time for further evaluation.

Citation: Nature Reviews Neurology volume 15, pages 501–518 (2019)

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