Lecanemab improves amyloid biomarkers but worsens neuronal/synaptic biomarkers. Should we question whether successful amyloid removal improves the biology that matters most? My take on the new study: lnkd.in/p/gfzXAHdj

The words of the Parkinson's literature:
“Accumulation”
“Replication”
"Prion-like"
“Propagation”
“Strains”
"Seeding"
They shape what we believe and do. Our patients’ lives depend on the language we adopt.

With Andrew Lees (@ajlees), in @GreenJournal:
doi.org/10.1212/WNL....

The “too late” defense of anti-amyloid trials has been tested in 6 preclinical #Alzheimer's trials (amyloid-positive, cognitively normal people). They range from futility to worsening. When does “early is better” become unfalsifiable?
lnkd.in/p/gYsFkWW5

With lecanemab, the real-world harms are clearly observed and include death; the cognitive benefit is counterfactual.
Here is the latest real-world report exemplifying this mismatch.
www.linkedin.com/posts/albert...

Less tau accumulation yet more clinical deterioration.

PROSPECT-ALZ offers a striking test of what happens when biomarkers move in the “right” direction but patients don't quite follow.

What does it take to falsify the tau-toxicity hypothesis?
www.linkedin.com/posts/albert...

Is the post–18-month steepening in the lecanemab and donanemab trials simply #Alzheimers natural “waterfall”? Unlikely, but let's assume it is true. What does that imply for claims of disease modification? lnkd.in/p/gzErdGEB