Just finished analyzing Dr. Mook-Jung's presentation from AAIC 2025, and this one has major implications for us.

The gut-brain highway is real. And for APOE4 carriers, it runs faster.

🔬 What the research showed:

Dr. Mook-Jung created vagal sensory neurons (the nerve fibers connecting gut to brain) from human stem cells with either APOE3 or APOE4.

When they tracked fluorescent-labeled amyloid beta and tau moving through these neurons, BOTH proteins traveled FASTER through E4 neurons compared to E3.

The study didn't tell us if having two copies (E4/E4 like some of us) makes it even faster—that's a critical question still unanswered.

🦠 It's not just proteins—it's bacteria too:

AD patients have more gram-negative bacteria in their guts. These bacteria produce LPS (lipopolysaccharide)—a toxin that activates inflammation.

They found LPS INSIDE amyloid plaques in AD patient brains. Where did it come from?

The gut. Via the vagus nerve.

When they cut the vagus nerve in AD mice, brain LPS levels dropped significantly.

⏰ And here's the kicker—timing:

In mice: Tau showed up in the GUT at 11 months, but wasn't in the BRAIN until 13 months.

In human PET scans: Early AD shows high tau in the brainstem (where vagus nerve enters) but low tau in hippocampus.

This suggests pathology might START in the gut and SPREAD to the brain.

💊 But there's hope—a therapeutic flip:

If the vagus nerve transports toxins FROM gut TO brain...

...could we use it to transport TREATMENTS from gut to brain?

Dr. Mook-Jung proposes packaging drugs in extracellular vesicles that vagal neurons will pick up and deliver to the brain—bypassing the blood-brain barrier.

Imagine oral Alzheimer's medications that actually reach your brain. That's the potential here.

Full deep dive (27 min):

Let's discuss. This could change how we think about early intervention.

—Kevin

Source:
Dr. In-hee Mook-Jung
"The Gut-Brain Axis in Alzheimer's Disease: Unraveling Pathogenesis and Exploring Novel Therapeutic Strategies"
AAIC 2025 Tuesday Plenary Session

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