Do not trade this blog as 4 billion years of evolution is against me and possibly even God laughs at it, He has a great sense of humor!

Do you remember these slides from CTAD 2017?

I decided to plot all patients in High Concentration Cohort from CTAD 2017 for the first 57 weeks.  From slide 29, we have the starting MMSE scores for 6 patients, all those who improved or barely declined.  The remaining patients declined very quickly but their initial scores are not known.

• I assumed that the mean MMSE score for all patients in the Cohort was 21 MMSE.
• The mean for the other 3 patients turned out to be 18.
• We know that 65 years old patients diagnosed on average 3 years after first symptoms should have on average MMSE 0 scores after 8.7 years, after declining from MMSE 20. Avg. Δ=-2.4 MMSE
• The 90 years old patients decline rapidly from 20 MMSE, and in 3.4 years we assume they have MMSE scores 0. Avg. Δ=-5.8 MMSE
• 75% of patients in High Concentration Cohort are APOE ε4 (rapidly declining)

So let’s see the graph:

Discussion:

• Three classes of patients are clearly visible.
• We can assume that the rapidly declining patients can be carries affected by all the detrimental conditions to improvements while dosing with Blarcaminase. 
• The 3 patients are just 30% of the Cohort.  From CTAD 2019 presentation we know that 75% ~6 patients are carriers of APOE e4.  In the general population ~50%.
• These numbers suggest that Blarcamenise helps even patients carrying the APOE e4 gene, the most destructive form of the gene connected with a specific form of amyloid plaque. 
• The number of 30% of rapid decliners is in line with SIGMAR1 mutation prevalence in the general population. Yet $AVXL did not have SIGMAR1 info on 11 patients, as of 2019 this information is only provided for the 21 patients who are currently enrolled in the Phase2a extension. I bet that as of 2019 the 3 patients are dropouts, so it is highly likely they had the SIGMAR1 mutation. 
• There is a disparity between the 75% of patients, either 6 or 7 carriers of APOE e4 of 9, and 60% of patients who are helped by Blarcamesine.  If indeed the SIGMAR1 mutation is the harbinger of the worst outcome so that the 3 patients could be carries of all the “bad” genes that makes at least 4 remaining patients be APOE e4 carriers, then Blarcamesine lifts this disadvantage.  
• The only conclusion that I can, in light of the point above, make is that the plaque theory of Alzheimer’s is not identifying the prime cause, so homeostasis might be a better candidate for it.