Thread by @MadhavThambiset

1/n 🧵@LillyPad deserves credit for reporting TRAILBLAZER #donanemab results quickly Their blood biomarker results tinyurl.com/bdewaf7b show for the 1st time relationship between change in plasma NfL & brain volume @ProfRobHoward @pash22 @JohnCendpts @AlbertoEspay @Dereklowe

2/n I have long believed that NfL, a marker of neurodegeneration, will track with accelerated brain atrophy in amyloid lowering Rx including #donanemab👇 This indeed appears to be the case. NfL shows significant correlation with change in whole brain volume (R = –0.1710; P =0.03)

3/n Importantly, increase in plasma NfL levels are associated with less slowing in the primary endpoint iADRS scores at week 76 ie worse clinical outcomes (R = –0.182 [95% CI, –0.322 to –0.035];P = 0.02). Caveat; I am always worried if I am interpreting the negative R correctly.

4/n Additional questions I wish @LillyPad had asked:
i) What is the relationship of ARIAE/H to NfL?
ii) How long-lasting are the changes in brain volume after stopping #donanemab?
iii) What is the association between plasma NfL and brain volume loss in the Rx group alone?

5/n These results have important implications. Despite amyloid lowering and a Rx effect lower than the prespecified minimal important difference (MCID), persistent increase in plasma NfL levels suggests that ongoing Neurodegeneration was not slowed by #donanemab

6/n Together with accelerated brain volume loss and an association with less slowing of cognitive decline, increase in plasma NfL levels may suggest a hastening of neurodegeneration and/or clinical progression. This is a hypothesis that can be tested in longer studies and

7/n potentially with existing data if they are made publicly available to researchers. It serves our patients interests to have these results published as @LillyPad has done and also to make them accessible to all investigators.