I agree it is worth measuring although my preferred lab that has a lot of biomarkers for a good price does not include it.
I also agree that the function of the immune system is key, but you do need some WBCs. My WBC is always under 3G (billions of cells per litre), at times it goes under 2G and then the lab has to phone me up.
You are right that people with higher WBC tend to be more inflamed. With me CRP is often too low to measure at 0.15mg/L.
My point about dosing is not daily vs weekly, but weekly vs fortnightly or even my high dose, but really infrequently.
In other words I don’t think we disagree much if at all.
Alzheimer’s disease (AD) is a predominant form of dementia in elderly. In sporadic AD and in families with higher risk of AD, correlation with apolipoprotein E4 (APOE) allele expression has been found. How APOE4 induces its pathological effects is still unclear. Several studies indicate that autophagy, a major degradation pathway trough the lysosome, may be compromised in AD. Here we studied, the effects of APOE isoforms expression in microglia cells. By using an in-situ model, the clearance of Aβ plaques from brain sections of transgenic 5xFAD mice by the APOE expressing microglia was examined. The results show that APOE4 microglia has Impairment In clearance of insoluble Aβ plaques as compared to APOE3 and APOE2 microglia. Furthermore, APOE4 affect the uptake of soluble Aβ. We found that microglia expressing APOE4 exhibit reduced autophagic flux as compared to those expressing APOE3. The autophagy inhibitor chloroquine also blocked Aβ plaque uptake in APOE3 expressing cells. Furthermore, we found that APOE4 expressing microglia have altered mitochondrial dynamics protein expression, mitochondrial morphology and mitochondrial activity compared to those expressing APOE2, and APOE3. Rapamycin treatment corrected Mitochondrial Membrane Potential in APOE4-expressing cells. Taken together, these findings suggest that APOE4 impairs the activation of autophagy, mitophagy, and Aβ clearance and that autophagy-inducing treatments, such as rapamycin, can enhance autophagy and mitochondrial functions in APOE4 expressing microglia. Our results reveal a direct link between APOE4 to autophagy activity in microglia, suggesting that the pathological effects of APOE4 could be counteracted by pharmacological treatments inducing autophagy, such as rapamycin.
I just completed a 4 week course of 2mg every other day. I was trying to approximate the 1mg / day dosing used in the study, but I only have 2mg pills. Symptoms were mild. I felt a little sluggish toward the end of the month, especially at the gym. I also found that it took me several days to recover from a particular intensive leg workout. No mouth sores.
On the day after my last dose, I measured my blood levels of Rapamycin at Labcorp. My levels were 4.6 mg/dl.
My current plan is to take a month off and then go back to semi-monthly dosing. (I originally wrote this wrong as “bi-monthly”. I went back and edited.)
Given how easy this 4 week course was, I’m thinking to do it again in 3 or 4 months, unless new info comes to light or one of you convince me that it’s a bad idea.
I think the peak concentration matters, but also the trough matters. If you mean by “bi-monthly” taking it for a month every other month I think that has insufficient trough. Furthermore I think the peak is not that good either.
Thanks, John. I wrote that incorrectly and went back and edited. I meant semi-monthly - or more accurately ever other week. But, now I realized that I have caused more confusion in the way I wrote it.
I have actually been following your general protocol of a large dose every 2 weeks with nothing in between.
I’m now thinking to mix that up and maybe 2x or 3x per year, take a four week period of daily 1mg (or every other day with 2mg). Then I would take a few weeks off and go back to the bi-weekly (every other week) protocol.
BTW, I did some blood level testing at 6 hours after dosing. My numbers were:
2mg + GFJ = 9.6ng/dl
8mg w/o = 14.3ng/dl
I split the difference and have been doing 4mg w/ GFJ but have not gotten around to the blood work to see how that translates. I will try to do the blood work next time.
What do you think of this concept of doing a daily (or bi-daily dose) for four weeks, then taking a break, then going back to the usual pulsed protocol? I don’t know the reasoning behind Ai-line Ling’s decision to use daily 1mg dosing, but it seems that it has done some good and it does not seem like it did any harm.
I take a large dose less frequently than every 4 weeks. It is now two months and I have not yet rescheduled rapa. I think mTOR inhibition should be normal most of the time.