Figure 1. Diagram showing treatment and numbers of healthy (WT) and transgenic mice undergoing FMT via oral gavage. Young Tg-FY: Young Transgenic-Fed Young, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old.

Figure 1. Diagram showing treatment and numbers of healthy (WT) and transgenic mice undergoing FMT via oral gavage. Young Tg-FY: Young Transgenic-Fed Young, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old.

Figure 2. FMT treated mice show normalization of behavior approaching control levels on the elevated plus maze. Old Tg-FY groups (n = 8) show improvement in anxiety-related behavior with increased (a) Percentage of time spent in closed arms and (b) Ratio of Closed:Open arm entries. Young Tg-FY group (n = 8) showed overall decreased anxiety with (c) a small increase in Percentage of time spent in closed arms and (d) decreased Ratio of Closed:Open arm entries. Data is presented as mean ± SEM. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control, Young WT: Young Wildtype, Old WT: Old Wildtype.

Figure 2. FMT treated mice show normalization of behavior approaching control levels on the elevated plus maze. Old Tg-FY groups (n = 8) show improvement in anxiety-related behavior with increased (a) Percentage of time spent in closed arms and (b) Ratio of Closed:Open arm entries. Young Tg-FY group (n = 8) showed overall decreased anxiety with (c) a small increase in Percentage of time spent in closed arms and (d) decreased Ratio of Closed:Open arm entries. Data is presented as mean ± SEM. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control, Young WT: Young Wildtype, Old WT: Old Wildtype.

Figure 3. FMT treated mice show improved recognition and spatial memory levels in Novel Object Recognition test measured using Discrimination Index (DI). (a) Old Tg-FO (n = 8) and Old Tg-FY (n = 8) had increased Discrimination Index (Old Tg-FY p < 0.01 compared to Old Tg-Control (n = 7)). (b) Young Tg-FY also showed improved DI compared to Young Tg-Control (n = 8). WT values are presented for comparison only. Data is presented as mean ± SEM. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control, Young WT: Young Wildtype, Old WT: Old Wildtype.

Figure 3. FMT treated mice show improved recognition and spatial memory levels in Novel Object Recognition test measured using Discrimination Index (DI). (a) Old Tg-FO (n = 8) and Old Tg-FY (n = 8) had increased Discrimination Index (Old Tg-FY p < 0.01 compared to Old Tg-Control (n = 7)). (b) Young Tg-FY also showed improved DI compared to Young Tg-Control (n = 8). WT values are presented for comparison only. Data is presented as mean ± SEM. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control, Young WT: Young Wildtype, Old WT: Old Wildtype.

Figure 4. Spatial memory levels improved in Old treated mice in Forced Alternation Y-maze. Data is presented as mean ± SEM. Old Tg-FO (n = 8) and Old Tg-FY (n = 8) demonstrated increased (a) exploration time in Novel arm and (b) Ratio of Novel to Open arm entries (p < 0.05 compared to Old Tg-Control (n = 7)). (c,d) Young Tg-FY (n = 8) did not show improvement in FAY compared to Young Tg-Control (n = 7). WT values are presented for comparison only. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control, Young WT: Young Wildtype, Old WT: Old Wildtype.

Figure 4. Spatial memory levels improved in Old treated mice in Forced Alternation Y-maze. Data is presented as mean ± SEM. Old Tg-FO (n = 8) and Old Tg-FY (n = 8) demonstrated increased (a) exploration time in Novel arm and (b) Ratio of Novel to Open arm entries (p < 0.05 compared to Old Tg-Control (n = 7)). (c,d) Young Tg-FY (n = 8) did not show improvement in FAY compared to Young Tg-Control (n = 7). WT values are presented for comparison only. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control, Young WT: Young Wildtype, Old WT: Old Wildtype.

Figure 5. FMT resulted in decreased amyloid plaque burden in treated mice as seen in Thioflavin S—stained brain sections. (a) Old Tg-FO and Old Tg-FY both had reduced percentage amyloid plaque with a nearly 2-fold decrease in Old Tg-FO (p < 0.01) and Old Tg-FY mice (p < 0.01) as well as (b) fewer plaques in both groups of treated mice (Old Tg-FY p < 0.05). (c) Young Tg-FY mice also showed a reduced percentage area of amyloid plaques with (d) no difference seen in the number of plaques. (e) Old Tg-FY mice showed decreased numbers of varying plaque sizes as compared to both Old Tg-Control and Old Tg-FO while (f) Young Tg-FY also showed decreased numbers of all plaque sizes compared to Young Tg-Controls. (h) Old Tg-FO mice and (i) Old Tg-FY had lesser amyloid plaque burden compared to (g) Old Tg-Controls. Mature, compact plaques were more diffuse with less defined outlines following FMT. Although (k) Young Tg-FY mice did not demonstrate decreased plaque burden compared to (j) Young Tg-Control mice, plaque dispersal appeared similar to the Old treated mice. Data is presented as mean ± SEM. Scale bar = 50 μm. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control.

Figure 5. FMT resulted in decreased amyloid plaque burden in treated mice as seen in Thioflavin S—stained brain sections. (a) Old Tg-FO and Old Tg-FY both had reduced percentage amyloid plaque with a nearly 2-fold decrease in Old Tg-FO (p < 0.01) and Old Tg-FY mice (p < 0.01) as well as (b) fewer plaques in both groups of treated mice (Old Tg-FY p < 0.05). (c) Young Tg-FY mice also showed a reduced percentage area of amyloid plaques with (d) no difference seen in the number of plaques. (e) Old Tg-FY mice showed decreased numbers of varying plaque sizes as compared to both Old Tg-Control and Old Tg-FO while (f) Young Tg-FY also showed decreased numbers of all plaque sizes compared to Young Tg-Controls. (h) Old Tg-FO mice and (i) Old Tg-FY had lesser amyloid plaque burden compared to (g) Old Tg-Controls. Mature, compact plaques were more diffuse with less defined outlines following FMT. Although (k) Young Tg-FY mice did not demonstrate decreased plaque burden compared to (j) Young Tg-Control mice, plaque dispersal appeared similar to the Old treated mice. Data is presented as mean ± SEM. Scale bar = 50 μm. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control.

Figure 6. Cognition score based on behavioral study results compared to amyloid plaque burden shows donor age-dependent differences between treated mice groups. (a) Mice receiving fecal transplants from younger donors (Old Tg-FY) had higher cognition scores that correlated with lower amyloid loading compared to Old Tg-FO mice that received transplants from age-matched donors. (b) Young Tg-FY mice showed marginal decreases in amyloid load following treatment. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control.

Figure 6. Cognition score based on behavioral study results compared to amyloid plaque burden shows donor age-dependent differences between treated mice groups. (a) Mice receiving fecal transplants from younger donors (Old Tg-FY) had higher cognition scores that correlated with lower amyloid loading compared to Old Tg-FO mice that received transplants from age-matched donors. (b) Young Tg-FY mice showed marginal decreases in amyloid load following treatment. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control.

Table 1. Summary of difference in significance across experimental groups for behavioral studies experimental measures and Aβ loading. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, EPM: Elevated Plus Maze, NOR: Novel Object Recognition, FAY: Forced Alternation Y-maze.

Table 1. Summary of difference in significance across experimental groups for behavioral studies experimental measures and Aβ loading. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, EPM: Elevated Plus Maze, NOR: Novel Object Recognition, FAY: Forced Alternation Y-maze.

Experimental MeasureOld Tg-FOOld Tg-FYYoung Tg-FYEPMp = 0.687p = 0.056p = 0.470NORp = 0.065p = 0.002p = 0.409FAYp = 0.046p = 0.012p = 0.505Aβ (amyloid load;
plaque number)p = 0.010;
p = 0.060p = 0.010;
p = 0.045p = 0.359