The guide to
ApoE4: The Alzheimer's Gene
What it means to be a carrier
ApoE4 and brain health
What is the ApoE4 gene
narration
"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
narration
How ApoE4 increases Alzheimer's risk
Two copies of E4 (Homozygous):
One copy of E4 (Heterozygous):
2% of the population 60% increased risk
25% of the population 25% 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.
narration
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.
Expert Perspective
"We know that there are four significant risk factors for progression to dementia: [the] presence of amyloid, significant 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
Read more
Professor and the Vice Chair of Research, Barrow Neurological Institute
narration
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
narration
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. There are friends and social issues that matter. 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
Read more
ApoE4 carrier
narration
Image source: skin test: DISCERN™ Lumbar puncture: InlandImaging AI tools: RealResearch Retinal scan: JoVE Journal
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
Exercise
Healthy sleep
Cognitive engagement
narration
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
Scientist and Chair of Genetic Medicine, Cornell University
Read more
narration
Want to learn more?
Visit
beingpatient.com
for the latest news and information on brain health and Alzheimer's disease
narration
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
AI technologies help analyze data from various sources, such as blood samples, speech patterns, and genetic profiles to enable early detection.
- Lorem ipsum dolor sit amet.
- Consectetur adipiscing elit.
- Sed do eiusmod tempor incididunt ut.
Read more on beingpatient.com
Lifelong learning and mental stimulation
Social connections and stress management
Helps clear beta-amyloid plaques from the brain. Improves cognitive function.
Blood tests reveal Alzheimer’s biomarkers, such as beta-amyloid and tau proteins.
FIVE thiNGS YOU NEED TO KNOW ABOUT BLOOD TESTS
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Skin tests promise to differentiate Alzheimer’s from other dementias with high accuracy, reinforcing the diagnosis.
Read more on Being Patient
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Dementia
Normal
Image soruce: JoVE Journal
Retinal scans look for changes in the retina that may reveal abnormalities within the brain.
- Lorem ipsum dolor sit amet.
- Consectetur adipiscing elit.
- Sed do eiusmod tempor incididunt ut.
Read more on beingpatient.com
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Lumbar puncture extracts cerebrospinal fluid to identify biomarkers like beta-amyloid and tau proteins.
- Lorem ipsum dolor sit amet.
- Consectetur adipiscing elit.
- Sed do eiusmod tempor incididunt ut.
CT and MRI scans look for abnormalities, while PET scans can detect beta-amyloid plaque.
Read more on beingpatient.com
Aerobic and resistance training. Low impact exercises — such as walking 4,000 steps a day.
Mediterranean-style diets are associated with a lower risk of dementia. DASH diet focuses on whole grains, fruits, vegetables, lean protein, and low-fat dairy.
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Lumbar puncture extracts cerebrospinal fluid to identify biomarkers like beta-amyloid and tau proteins.
- Lorem ipsum dolor sit amet.
- Consectetur adipiscing elit.
- Sed do eiusmod tempor incididunt ut.
CT and MRI scans look for abnormalities, while PET scans can detect beta-amyloid plaque.
Read more on beingpatient.com
Blood tests reveal Alzheimer’s biomarkers, such as beta-amyloid and tau proteins.
FIVE thiNGS YOU NEED TO KNOW ABOUT BLOOD TESTS
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Lumbar puncture extracts cerebrospinal fluid to identify biomarkers like beta-amyloid and tau proteins.
- Lorem ipsum dolor sit amet.
- Consectetur adipiscing elit.
- Sed do eiusmod tempor incididunt ut.
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Skin tests promise to differentiate Alzheimer’s from other dementias with high accuracy, reinforcing the diagnosis.
Read more on Being Patient
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Dementia
Normal
Image soruce: JoVE Journal
Retinal scans look for changes in the retina that may reveal abnormalities within the brain.
- Lorem ipsum dolor sit amet.
- Consectetur adipiscing elit.
- Sed do eiusmod tempor incididunt ut.
Read more on beingpatient.com
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
AI technologies help analyze data from various sources, such as blood samples, speech patterns, and genetic profiles to enable early detection.
- Lorem ipsum dolor sit amet.
- Consectetur adipiscing elit.
- Sed do eiusmod tempor incididunt ut.
Read more on beingpatient.com
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Lumbar puncture extracts cerebrospinal fluid to identify biomarkers like beta-amyloid and tau proteins.
- Lorem ipsum dolor sit amet.
- Consectetur adipiscing elit.
- Sed do eiusmod tempor incididunt ut.
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Created on August 29, 2024
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Transcript
The guide to
ApoE4: The Alzheimer's Gene
What it means to be a carrier
ApoE4 and brain health
What is the ApoE4 gene
narration
"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
narration
How ApoE4 increases Alzheimer's risk
Two copies of E4 (Homozygous):
One copy of E4 (Heterozygous):
2% of the population 60% increased risk
25% of the population 25% 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.
narration
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.
Expert Perspective
"We know that there are four significant risk factors for progression to dementia: [the] presence of amyloid, significant 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
Read more
Professor and the Vice Chair of Research, Barrow Neurological Institute
narration
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
narration
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. There are friends and social issues that matter. 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
Read more
ApoE4 carrier
narration
Image source: skin test: DISCERN™ Lumbar puncture: InlandImaging AI tools: RealResearch Retinal scan: JoVE Journal
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
Exercise
Healthy sleep
Cognitive engagement
narration
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
Scientist and Chair of Genetic Medicine, Cornell University
Read more
narration
Want to learn more?
Visit
beingpatient.com
for the latest news and information on brain health and Alzheimer's disease
narration
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
AI technologies help analyze data from various sources, such as blood samples, speech patterns, and genetic profiles to enable early detection.
Read more on beingpatient.com
Lifelong learning and mental stimulation
Social connections and stress management
Helps clear beta-amyloid plaques from the brain. Improves cognitive function.
Blood tests reveal Alzheimer’s biomarkers, such as beta-amyloid and tau proteins.
FIVE thiNGS YOU NEED TO KNOW ABOUT BLOOD TESTS
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Skin tests promise to differentiate Alzheimer’s from other dementias with high accuracy, reinforcing the diagnosis.
Read more on Being Patient
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Dementia
Normal
Image soruce: JoVE Journal
Retinal scans look for changes in the retina that may reveal abnormalities within the brain.
Read more on beingpatient.com
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Lumbar puncture extracts cerebrospinal fluid to identify biomarkers like beta-amyloid and tau proteins.
CT and MRI scans look for abnormalities, while PET scans can detect beta-amyloid plaque.
Read more on beingpatient.com
Aerobic and resistance training. Low impact exercises — such as walking 4,000 steps a day.
Mediterranean-style diets are associated with a lower risk of dementia. DASH diet focuses on whole grains, fruits, vegetables, lean protein, and low-fat dairy.
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Lumbar puncture extracts cerebrospinal fluid to identify biomarkers like beta-amyloid and tau proteins.
CT and MRI scans look for abnormalities, while PET scans can detect beta-amyloid plaque.
Read more on beingpatient.com
Blood tests reveal Alzheimer’s biomarkers, such as beta-amyloid and tau proteins.
FIVE thiNGS YOU NEED TO KNOW ABOUT BLOOD TESTS
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Lumbar puncture extracts cerebrospinal fluid to identify biomarkers like beta-amyloid and tau proteins.
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Skin tests promise to differentiate Alzheimer’s from other dementias with high accuracy, reinforcing the diagnosis.
Read more on Being Patient
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Dementia
Normal
Image soruce: JoVE Journal
Retinal scans look for changes in the retina that may reveal abnormalities within the brain.
Read more on beingpatient.com
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
AI technologies help analyze data from various sources, such as blood samples, speech patterns, and genetic profiles to enable early detection.
Read more on beingpatient.com
Consectetur adipiscing elit
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod.
Lumbar puncture extracts cerebrospinal fluid to identify biomarkers like beta-amyloid and tau proteins.