ApoE4: The Alzheimer's Gene
What is the ApoE4 gene
What it means to be a carrier
Protecting your brain
ApoE4 and brain health
"The Alzheimer's gene"
The ApoE (apolipoprotein E) gene — which helps regulate cholesterol and fat metabolism — has three main variants, known as alleles. These are: E2, E3, and E4. Everyone inherits two copies of ApoE — one from each parent.
ApoE variants and Alzheimer's risk:The variant ApoE4 is one of the strongest genetic risk factors for late-onset Alzheimer’s.
E2
E4
E3
reduced risk
neutral risk
higher risk
Return
Next
How ApoE4 increases Alzheimer's risk
One copy of E4 (Heterozygous):
25% of the population 25% increased risk
Two copies of E4 (Homozygous):
2% of the population 60% increased risk
Having two copies of ApoE4 means you have inherited a single copy from each parent. One in every six people living with Alzheimer's disease is also E4 homozygous. However, carrying two copies doesn't guanrantee Alzheimer's.
Return
Next
What ApoE4 can teach us
Dr. Marwan Sabbagh explained to Being Patient how the presence of a genetic variants such as ApoE4 can impact not only our risk of developing Alzheimer's disease, but our risk of side effects from Alzheimer's drugs.
"We know that there are four significant risk factors for progression to dementia: [the] presence of amyloid, neurodegeneration on your MRI, bottoming out on your neuropsych testings, and the ApoE4 carrier status. So, if you are not an ApoE4 carrier, your risk of progression to dementia is six percent per year. If you’re an ApoE4 carrier, it’s 17 percent per year, so it is a significant predictor of future decline."
Dr. Marwan Sabbagh
Barrow Neurological Institute
Read more
Return
Next
ApoE4 and Alzheimer's "mab" drugs
New Alzheimer's monoclonal antibody drugs — like Leqembi and Kisunla — aim to reduce amyloid plaque accumulation in the brain to slow disease progression. ApoE4 carriers face higher risk of potentially dangerous side effects with these treatments, including higher risk of ARIA (brain swelling or brain bleeds). In the UK, regulators have approved Leqembi — but not for people who carry two copies of ApoE4.
Read more
Return
Next
ApoE4 perspectives
Today, it's much easier for someone to learn whether they carry genes that increase their Alzheimer's risk via genetic testing.
"For those of us who inherited two copies of 'the Alzheimer’s gene, we are already familiar with a landscape of uncertainty... and for now, I have chosen a path forward in my line of sight. There is family I love in another city, and a book I have to write. Their importance eclipses the questions of whether my cognition will be intact two years from now, whether I will ever see Greece or Scotland. I will unapologetically protect myself [from Alzheimer's through lifestyle interventions] so that I can take care of what is immediate and pressing."
Deborah Fries
ApoE4 carrier
Read more
Return
Next
Lifestyle changes for Alzheimer's prevention
For people who carry the ApoE4 variant, doctors and scientists recommend science-backed healthy lifestyle modifications — as well as monitoring for early signs of cognitive decline.
Brain healthy diets
Healthy sleep
Exercise
Cognitive engagement
Return
Next
Gene therapy
Gene therapies may be a solution in the future to reduce risk of developing Alzheimer’s, including de-risking the gene from an E4 copy to an E2 copy.
"There’s a lot of work that’s going on throughout the world in terms of gene therapy. Many of these gene therapies work by changing the expression of a specific gene by trafficking a brand new copy of a healthy gene into brain cells or drugs that affect how much a gene is activated. These forms of gene therapy do not change the underlying genetic code."
Ronald Crystal
Cornell University
Read more
Return
Next
Want to learn more?
Visit
beingpatient.com
for the latest news and information on brain health and Alzheimer's disease
Return
Mediterranean-style diets are associated with a lower risk of dementia. The DASH diet focuses on whole grains, fruits, vegetables, lean protein, and low-fat dairy.
Lifelong learning and mental stimulation Social connections and stress management
E3, the most common variant, neither increases nor decreases the risk of Alzheimer’s.
E4 is associated with increased Alzheimer's risk.
Healthy sleep helps clear beta-amyloid plaques from the brain and improves cognitive function.
E2 may provide protection against Alzheimer’s. Roughly 5% to 10% of people have this allele.
Aerobic and resistance training Low impact exercises — such as walking 4,000 steps a day
ApoE4 the Alzheimer's Gene
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Transcript
ApoE4: The Alzheimer's Gene
What is the ApoE4 gene
What it means to be a carrier
Protecting your brain
ApoE4 and brain health
"The Alzheimer's gene"
The ApoE (apolipoprotein E) gene — which helps regulate cholesterol and fat metabolism — has three main variants, known as alleles. These are: E2, E3, and E4. Everyone inherits two copies of ApoE — one from each parent.
ApoE variants and Alzheimer's risk:The variant ApoE4 is one of the strongest genetic risk factors for late-onset Alzheimer’s.
E2
E4
E3
reduced risk
neutral risk
higher risk
Return
Next
How ApoE4 increases Alzheimer's risk
One copy of E4 (Heterozygous):
25% of the population 25% increased risk
Two copies of E4 (Homozygous):
2% of the population 60% increased risk
Having two copies of ApoE4 means you have inherited a single copy from each parent. One in every six people living with Alzheimer's disease is also E4 homozygous. However, carrying two copies doesn't guanrantee Alzheimer's.
Return
Next
What ApoE4 can teach us
Dr. Marwan Sabbagh explained to Being Patient how the presence of a genetic variants such as ApoE4 can impact not only our risk of developing Alzheimer's disease, but our risk of side effects from Alzheimer's drugs.
"We know that there are four significant risk factors for progression to dementia: [the] presence of amyloid, neurodegeneration on your MRI, bottoming out on your neuropsych testings, and the ApoE4 carrier status. So, if you are not an ApoE4 carrier, your risk of progression to dementia is six percent per year. If you’re an ApoE4 carrier, it’s 17 percent per year, so it is a significant predictor of future decline."
Dr. Marwan Sabbagh
Barrow Neurological Institute
Read more
Return
Next
ApoE4 and Alzheimer's "mab" drugs
New Alzheimer's monoclonal antibody drugs — like Leqembi and Kisunla — aim to reduce amyloid plaque accumulation in the brain to slow disease progression. ApoE4 carriers face higher risk of potentially dangerous side effects with these treatments, including higher risk of ARIA (brain swelling or brain bleeds). In the UK, regulators have approved Leqembi — but not for people who carry two copies of ApoE4.
Read more
Return
Next
ApoE4 perspectives
Today, it's much easier for someone to learn whether they carry genes that increase their Alzheimer's risk via genetic testing.
"For those of us who inherited two copies of 'the Alzheimer’s gene, we are already familiar with a landscape of uncertainty... and for now, I have chosen a path forward in my line of sight. There is family I love in another city, and a book I have to write. Their importance eclipses the questions of whether my cognition will be intact two years from now, whether I will ever see Greece or Scotland. I will unapologetically protect myself [from Alzheimer's through lifestyle interventions] so that I can take care of what is immediate and pressing."
Deborah Fries
ApoE4 carrier
Read more
Return
Next
Lifestyle changes for Alzheimer's prevention
For people who carry the ApoE4 variant, doctors and scientists recommend science-backed healthy lifestyle modifications — as well as monitoring for early signs of cognitive decline.
Brain healthy diets
Healthy sleep
Exercise
Cognitive engagement
Return
Next
Gene therapy
Gene therapies may be a solution in the future to reduce risk of developing Alzheimer’s, including de-risking the gene from an E4 copy to an E2 copy.
"There’s a lot of work that’s going on throughout the world in terms of gene therapy. Many of these gene therapies work by changing the expression of a specific gene by trafficking a brand new copy of a healthy gene into brain cells or drugs that affect how much a gene is activated. These forms of gene therapy do not change the underlying genetic code."
Ronald Crystal
Cornell University
Read more
Return
Next
Want to learn more?
Visit
beingpatient.com
for the latest news and information on brain health and Alzheimer's disease
Return
Mediterranean-style diets are associated with a lower risk of dementia. The DASH diet focuses on whole grains, fruits, vegetables, lean protein, and low-fat dairy.
Lifelong learning and mental stimulation Social connections and stress management
E3, the most common variant, neither increases nor decreases the risk of Alzheimer’s.
E4 is associated with increased Alzheimer's risk.
Healthy sleep helps clear beta-amyloid plaques from the brain and improves cognitive function.
E2 may provide protection against Alzheimer’s. Roughly 5% to 10% of people have this allele.
Aerobic and resistance training Low impact exercises — such as walking 4,000 steps a day