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Rhonda Patrick (@foundmyfitness) is the host of the FoundMyFitness podcast (Podcast Notes) Rhonda was actually Kevin’s first podcast guest ApoE4 Predicts Alzheimer’s Disease Risk ApoE is a gene There are four different isoforms (AKA alleles) of ApoE – they’re referred to as 1, 2, 3, and 4 (but most of the time you’ll find 2, 3 and 4) Everybody has two copies of the ApoE gene (one from mom and one from dad) Most people have two copies of ApoE3 People with an ApoE4 allele have an increased risk of Alzheimer’s disease (you can use 23andMe to see your ApoE phenotype) People with one allele have a 2-fold higher risk of Alzheimer’s disease, while those two alleles have a 10-15-fold higher risk Around 25% of the population has at least one copy of ApoE4 65-85% of the people diagnosed with Alzheimer disease have at least one copy of ApoE4 DHA Transport Across the Blood-Brain Barrier The blood-brain barrier (BBB) is lined with endothelial cells, separated by tight junctions As we age, these tight junctions become compromised – this becomes even more of an issue in people with an ApoE4 allele DHA is one of the predominant omega-3s, primarily found in marine sources The only type of DHA that crosses the blood-brain barrier is DHA bound to albumin (a protein found in the bloodstream which transports a variety of molecules to tissue throughout the body) There are two forms of DHA bound to albumin: Free DHA, DHA that’s not esterified (it’s not attached to anything besides albumin) This complex gets transported across the BBB via passive diffusion, but because normal aging and ApoE4 both disrupt these tight junctions, this diffusion process can be compromised The phospholipid form of DHA, known as lysophosphatidylcholine DHA (AKA lysoPC DHA) This complex is transported across the BBB using a specific transporter
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The protective effects of NAC were mediated through two primary mechanisms: the inhibition of CDK5-dynamin-related protein 1 (DRP1) signaling and the modulation of the glutathione peroxidase 1 (GPx1)-nuclear factor kappa B (NF-κB) pathway
