Research and videos
APOE4 gene therapies and APOE4-lowering drugs: the research and Kevin's videos
When will gene therapies or APOE4-lowering drugs (CRISPR, antisense) arrive, and will they work?
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This page has no results from Phoenix members yet. It shows what published research says, and what Kevin and the experts say in his videos.
See what Phoenix members have measuredWhen will gene therapies or APOE4-lowering drugs (CRISPR, antisense) arrive, and will they work?
Too early to say. In mice, lowering APOE4 or switching it to APOE2 reduces amyloid and can improve memory, and rare people whose APOE4 copy is broken have stayed healthy into old age. No human trial has yet shown a benefit, and getting these treatments into the brain safely is the hurdle.
What the research says
Grade DAPOE4-specific evidence: yes
Too early to say: APOE4-lowering and APOE2 gene approaches work in mice and are supported by rare human genetics, but no human trial has shown a benefit yet.
Key studies
Huynh 2017, NeuronGrade D
Animal or lab study
Animal study: lowering APOE with antisense drugs before plaques formed reduced amyloid in mice.
Read on PubMed (opens in a new tab)Golden 2025, Nat NeurosciGrade D
Animal or lab study
Animal study: switching APOE4 to APOE2 in mouse astrocytes improved memory and lowered amyloid.
Read on PubMed (opens in a new tab)Chemparathy 2024, NeuronGrade D
People with one broken APOE copy lived long; two APOE3/4 carriers whose E4 copy was broken stayed free of amyloid.
Read on PubMed (opens in a new tab)
3 more key studies
Arboleda-Velasquez 2019, Nat MedGrade D
Case report: a rare APOE3 Christchurch variant delayed inherited Alzheimer's by decades.
Read on PubMed (opens in a new tab)Kantor 2024, Nat Commun
Animal or lab study
Lab and mouse study: a non-cutting CRISPR tool delivered by one AAV turned down APOE expression.
Read on PubMed (opens in a new tab)Rosenberg 2018, Hum Gene Ther Clin Dev
Animal or lab study
Preclinical work behind the APOE2 gene therapy (AAVrh.10) now in early human testing.
Read on PubMed (opens in a new tab)
What Kevin and experts say
4 passages for, 1 with a caution, 4 also discussed
Now showing: Dr. Brandon Colby · 51:09
Open on YouTube (opens in a new tab)For4 passages
Gene editing could one day turn APOE4 into APOE2.
“Changing two would take a person from four to two.”
Dr. Brandon Colby, Physician, founder and CEO of Sequencing.com
Lowering APOE in mice reduced plaque and inflammation.
“Whether you reduce APOE using gene editing, synthetic antibodies or anti-sense [oligonucleotide], you constantly see the same outcome.”
Dr. Kevin Tran, Founder of The Phoenix Community, Doctor of Pharmacy, APOE4/4 carrier
Partly lowering APOE4 may buy years.
“you don't need to silence both copies to seek benefits”
Dr. Kevin Tran, Founder of The Phoenix Community, Doctor of Pharmacy, APOE4/4 carrier
Silencing APOE4 cut tau and inflammation in lab cells.
“We were able to detect reduction in [phosphorylated tau] expression.”
Dr. Ornit Chiba-Falek, Duke University, APOE4 epigenome therapy (AAIC APOE and Lipid Biology 2025)
With a caution1 passage
APOE editing works only partly, and only in mice so far.
“[They] actually already did it in some mice models only a very small percentage of some brain cells”
Dr. Kevin Tran, Founder of The Phoenix Community, Doctor of Pharmacy, APOE4/4 carrier
Also discussed4 passages
Gene editing carries irreversible risks; it suits higher-risk people.
“the problem with editing is you can't really do a control Z or return”
Dr. Kevin Tran, Founder of The Phoenix Community, Doctor of Pharmacy, APOE4/4 carrier
In mice, no APOE meant no plaques.
“When they simply removed APOE by crossing these mice to APOE knockout mice, this blocked the formation of fibrillar [amyloid].”
Dr. David Holtzman, Alzheimer's researcher, Washington University in St. Louis (conference clips)
Which cell type gets the switch changes the result.
“when they made the same genetic switch but only in [microglia amyloid] still went down but memory didn't improve.”
Dr. Kevin Tran, Founder of The Phoenix Community, Doctor of Pharmacy, APOE4/4 carrier
Gene "dimming" of APOE4 is early lab research.
Dr. Kevin Tran
Watch the Short on YouTube (opens in a new tab)
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