Alzheimer’s Disease, DHA, and APOE4

Very Brief Summary:

  • DHA is an essential omega-3 fatty acid and plays a vital role in the prevention and reversal of cognitive decline and Alzheimer’s Disease
  • The form of DHA found in fish, fish roe, and krill oil is primarily in phospholipid form and this form is broken down to DHA-lysoPC
  • The form of DHA found in DHA/fish oil supplements is not in phospholipid form and is primarily broken down to free DHA
  • APOE4 carriers have impaired free DHA transport into the brain because of APOE4-mediated degradation of the blood brain barrier, but this degradation does not impair how DHA-lysoPC enters the brain
  • Dr. Rhonda Patrick proposes that consuming DHA in phospholipid form may be a strategy for APOE4 carriers to get DHA into the brain and prevent APOE4-associated Alzheimer’s Disease, which is found in fish, fish roe, and krill oil but not in fish oil supplements

Not-So-Brief Summary:

What is APOE?

Three Primary Pathological Hallmarks of AD:

1. Extracellular Amyloid-ß Plaques

In short: chronic activation of our brain’s immune cells leads to amyloid-ß plaque build up, and clearance is impaired in APOE4 carriers.

2. Intracellular Neurofibrillary Tangles:

In short: aggregates of tau proteins form tau tangles inside neurons and result in long-term memory loss and neuronal cell death.

3. Reduced Brain Glucose Uptake:

In short: APOE4 carriers have reduced brain glucose uptake (which is more pronounced as we age) because APOE4 downregulates the transport of glucose into the brain.

How DHA acts on all three of these pathologies:

Low levels of DHA promote all three pathological hallmarks of AD

Normal/high levels of DHA prevent or reverse all three pathological hallmarks of AD

Why would fish improve cognitive function in APOE4 carriers but supplementing with DHA does not?

In short: the type of DHA found in fish, fish roe, and krill oil has a better chance of getting into the brain of APOE4 carriers.

In short: the type of DHA in fish oil supplements can not adequately enter the brain in APOE4 carriers, especially in older individuals.

Metabolism of DHA in phospholipid form (fish, fish roe, krill oil):

Metabolism of DHA in ethyl ester and triglyceride form (DHA & Fish oil supplements):

IN SUMMARY: APOE4 limits the transport of free DHA (from DHA supplements) into the brain, therefore consuming DHA in phospholipid form to generate DHA-lysoPC (e.g. fish, fish roe, and krill oil) may bypass this faulty transport in APOE4 carriers.

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Kristi Storoschuk

Kristi Storoschuk

Science writer with a focus on ketogenic nutrition and metabolic therapies. www.getoldslowly.com