Nick Fox making the case that excess brain volume loss associated with Lecanemab (or other effective mAB’s) is associated with the removal of “space-occupying” structures, as amyloid plaques occupy ~6-8% of the cortex in autopsy studies. #AAIC24

Homozygosity for R47H in TREM2 and the Risk of Alzheimer’s Disease Another AD-relevant publication @NEJM this week. TREM2 variants like R47H may induce partial loss of function by interfering with binding of ligands such as low-density lipoprotein (LDL), apolipoprotein E (ApoE), and clusterin (CLU). R47H homozygosity: 1⃣ Does not contribute to Aβ overproduction but instead disrupts Aβ clearance 2⃣ Leads to the accumulation of amyloid plaques 3⃣ Is associated with a high risk of symptomatic Alzheimer’s disease (OR=97.1; 95% CI=23.5-401.1). Conclusion: "The high risk in R47H homozygotes underscores the necessity for early intervention if treatments such as Aβ-removing antibodies are shown to have efficacy at the preclinical stage." Link to paper > nejm.org/doi/pdf/10.1056/NEJ…