A Small Molecule p75NTR Ligand, LM11A-31, Reverses Cholinergic Neurite Dystrophy in Alzheimer's Disease Mouse Models with Mid- to Late-Stage Disease Progression
Figure 7
LM11A-31 prevents atrophy of cholinergic neurites in basal forebrain of late-stage APPL/S mice.
Representative photomicrographs show ChAT-immunostained neurons in the basal forebrain of (A) WT Veh, (B) APPL/S (APP) Veh, and (C) APP-31 mice at 13–14 months of age. Arrowheads indicate the distal part of neurites. Scale bar in A = 40 µm. Below each photomicrograph are reconstructed drawings from Neurolucida tracings of two ChAT-stained neurons per treatment group indicated by the arrowhead in the photomicrograph. Scale bar in drawing under A = 40 µm. Quantitative analysis showed that treating late-stage APPL/S mice with LM11A-31 for 1 month prevented the decreases in (D) length, (E) surface area, and (F) branching of cholinergic neurites in basal forebrain, although the latter measure did not reach statistical significance. Statistical significance was determined using an ANOVA with Dunnett's post-hoc test and/or two-tailed Student's t-test for BFCN neurite degeneration and, for branching, a 2×2 contingency table with Fisher's exact test (WT Veh, n = 5 mice; APP Veh, n = 4; APP-31, n = 5). *p<0.05, **p≤0.01 and ***p<0.001 vs. WT Veh; +p<0.05 and ++p≤0.01 vs. APP Veh.