LM11A-31 prevents and/or reverses basal forebrain cholinergic neurite atrophy in mid-stage APPL/S mice.

Representative photomicrographs show ChAT-immunostained neurons in VDB of the basal forebrain of (A) WT Veh, (B) WT LM11A-31 (-31), (C) APPL/S (APP) Veh, and (D) APP-31 mice at 9–11 months of age. Arrowheads indicate the distal part of neurites. Below each photomicrograph are reconstructed drawings from Neurolucida tracings of two ChAT-stained neurons per treatment group. The left drawing is the neurite and corresponding soma indicated by the arrowhead in the photomicrograph (orientations were altered). The right drawing is of a cell outside the field displayed in the photomicrograph but within the field analyzed. Scale bar in A = 20 µm and also applies to the line drawings. Quantification indicates that treating APPL/S mice with LM11A-31 for 3 months increases the (E) length, (F) area occupied by, and (G) branching of BFCN neurites compared to those given vehicle. Statistical significance was determined using an ANOVA with Dunnett's post-hoc test and, for branching, a 2×2 contingency table with Fisher's exact test (WT Veh, n = 9 mice; WT-31, n = 10; APP Veh, n = 10; APP-31, n = 9). **p≤0.01 and ***p<0.001 vs. WT Veh; +p≤0.05 and ++p≤0.01 vs. APP Veh.