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 9
LM11A-31 reverses dystrophy of cholinergic neurites that occurs with aging in APPL/S mice.
Quantitative analysis of the effect of aging showed that 13–14 month old vehicle-treated APPL/S (APP) mice had ChAT neurites in basal forebrain with decreased (A) length and (B) area and had dystrophic neurite clusters in cortex that occupied more area (C) and were larger (D) compared to the 9–11 month old APP Veh mice. In 13–14 month old APP mice, LM11A-31 increased the length and area of ChAT neurites in basal forebrain while decreasing the area of cortical dystrophic neurites compared to vehicle-treated mice (A–D; absolute numbers shown in Figs. 4 and 5). The effect of LM11A-31 in the basal forebrain was a reversal as neurite length (A) and area (B) were significantly greater in 13–14 month old APP-31 mice than 9–11 month old APP Veh mice. In the cortex, LM11A-31 did not reverse the area occupied by dystrophic neurites as 13–14 month old APP-31 mice still had significantly larger clusters than 9–11 month old APP Veh mice (C, D). Results are expressed as a percentage of the 9–11 month old APP Veh group. Statistical significance was determined using one-tailed Student's t-test (For 9–11 month old APP Veh n = 10; For 13–14 month group: APP Veh, n = 4; APP-31, n = 5). *p≤0.05, **p≤0.005 and ***p≤0.001 vs. 9–11 month old APP Veh; +p≤0.05 and ++p≤0.01 vs. 13–14 month old APP Veh.