The woman who defied the Alzheimer's Disease odds (and what it means for APOE4 carriers)

Phoenix friends,

Quick story that's been in my head:
Woman in Colombia. Has the mutation for early-onset Alzheimer's (PSEN1). Should have developed symptoms at 44.

Instead? Symptoms at 73.

Her secret: Two copies of the Christchurch variant.

But here's what's wild: her brain was FULL of plaques.

The variant didn't prevent them. It prevented what came after.
It blocked the tau cascade that actually destroys neurons.

This completely changes how we think about the amyloid-tau relationship.
Then I dug deeper in that conference and they covered the mechanism of action of two other protective variants:

• APOE2: Prevents amyloid from ever accumulating (like having a super-efficient garbage truck)

• Jacksonville (V236E): Improves lipid transport and prevents APOE aggregation (fixes the brain's delivery system)

You are probably thinking: “Yeah Kevin, but I don’t have those protective genes. I carry ApoE4 and good for them, but what does it mean for me?”

Researchers aren’t just studying these protective genes out of curiosity. They want to understand how they work so they can mimic their effects and eventually develop new therapies.

Why this matters: Each variant works on a different part of the protein and targets a different disease mechanism. They're scattered across different protein domains—some affect receptor binding (N-terminal), others affect lipid binding (C-terminal). It's like having different tools that each fix a different part of the problem.

So what am I actually doing with this?
Still figuring it out, to be honest. But here's where my head is:

1. For amyloid: Really doubling down on sleep quality and anything that enhances glymphatic clearance. If APOE2 keeps the brain "clean," maybe we can mimic that with better waste removal.

2. For tau: This has me rethinking inflammation. The Christchurch variant seems to change how cells respond to stress. Cold exposure? Specific polyphenols? Still researching.

3. For lipid transport: DHA supplementation makes even more sense. So does everything around metabolic health.

The real question: Should we be targeting all three pathways instead of focusing over just one?

I made a video breaking down all three mechanisms

-Kevin

P.S. Should mention this isn't medical advice. I’m just sharing research I'm personally tracking for obvious reasons.