I just published a new conversation with Dr. Grant Fraser on APOE4 biomarkers, this time focused on markers that may suggest the brain/body is under stress: hs-CRP, ferritin, iron, oxidative stress, GGT, and some of the more "advanced" inflammatory/blood-brain-barrier markers people ask about.

Main takeaways from the discussion:

\- hs-CRP may run lower in APOE4 carriers for the same inflammatory burden, so Dr. Fraser likes a lower target than the standard "under 1." His practical target, especially for APOE4/4, is under 0.5 mg/L.

\- A single high hs-CRP value can be transient. Infection, dental inflammation, fasting, autoimmune flares, sleep apnea, visceral fat, etc. can all move it.

\- Ferritin matters because iron is a sweet-spot biomarker. Too low is bad for energy, cognition, muscles, and enzymes. Too high may increase oxidative stress and may be relevant to amyloid accumulation, especially in APOE4.

\- His practical ferritin target was roughly 40-80 ng/mL, with individual context.

\- Ferritin should be interpreted with hs-CRP because ferritin is also an inflammatory marker. If CRP is high, ferritin may look artificially high.

\- Blood donation can be useful for high ferritin, but he pushed back on the idea that frequent donation is a broad "detox" strategy.

\- GGT can reflect liver stress, alcohol/toxin burden, oxidative stress, and sometimes insulin resistance, but it was not as central as hs-CRP and ferritin.

\- On IL-6, TNF-alpha, MMP-9, MPO, fibrinogen, ADMA/SDMA, etc., his rule was basically: don't test it unless the result changes what you would actually do.



The part I personally found most useful was the "don't test what you don't know how to act on" rule. It's easy to keep adding biomarkers because they sound interesting, but the actionable core may be smaller than we think.



Curious how others here are tracking hs-CRP and ferritin. Do you use different targets because of APOE4?

APOE4 and hs-CRP, ferritin, iron, and why "normal" may not be optimal