1. Figure S1. Generation of AD/PNGFP+/+ Mice
a, b A representative image of a brain section from AD/PNGFP+/+ mice at 3 months old of age. High magnifications show GFP expression in the CA1 pyramidal neurons
c The experimental procedures show qPCR analysis of the PNGFP+/+ cells including dissection of CA1 hippocampus from AD/PNGFP+/+ mice, sorting PNGFP+/+ cells.

2. Figure S2. Application of LNA-BC1 Produces No Effects on APP mRNA Expression and BACE1 Activity in AD Mice
a APP mRNA was examined using qPCR. Data are mean ± SEM (n = 6 mice per group).
b BACE1 protein was examined using Western blots. Data are mean ± SEM (n = 6 mice per group).
c Catalytic activity of BACE1 was examined in the CA1 hippocampus of AD mice treated with multiple doses of saline, LNA-sBC1 or LNA-BC1. Data are mean ± SEM (n = 6 mice per group).
d Application of LNA-BC1 produces no change in the levels of a full-length APP in the non-transgenic control mice. A full-length APP was examined in the CA1 hippocampus of control mice treated with saline, or LNA-sBC1 or LNA-BC1. Data are mean ± SEM (n = 6 mice per group).

3. Figure S3. Application of Tat-FMRP61-79 Produces No Changes of BACE1 Activity in AD Mice.
a-d BACE1 activity in the CA1 hippocampus of AD mice at 3 or 9 months old of age was examined. AD mice were treated with multiple doses of Tat-sFMRP61-79 or Tat-FMRP Data are mean ± SEM (n = 5 mice per group).
e WB shows that there were no significant difference changes of α-secretase levels between application of Tat-FMRP and the control group.
f WB shows that the time-depend of the Tat-FMRP61-79.

4. Figure S4. Application of Tat-FMRP61-79 Did Not Alter Learning and Memory-unrelated Behaviors.
a Bar graphs show that distance moved and rearing counts in the open field tests are identical between genotypes. Data are mean ± SEM ( n = 9 mice per group).
b Bar graphs show that the performance for foot stay and fault on rotarod tests is comparable between genotypes. Data are mean ± SEM ( n = 9 mice per group).
c Bar graphs show that the CA1 neurons between genotypes. Data are mean ± SEM ( n = 9 mice per group).
d Bar graphs show that the genotypes stained with Fluoro-Jade. Data are mean ± SEM ( n = 9 mice per group).

5. Figure S5. Expression of BC1 Did Not Alter Learning and Memory-unrelated Behaviors and BACE1 Activity .
a Bar graphs show that distance moved and rearing counts in the open field tests are identical between genotypes. Data are mean ± SEM ( n = 11 mice per group).
b Bar graphs show that the performance for foot stay and fault on rotarod tests is comparable between genotypes. Data are mean ± SEM ( n = 11 mice per group).
c BACE1 activity in the CA1 hippocampus of PNeBC1+/+ and PNeBC1-/- mice at 6, 7, 8, or 9 months old of age was examined. Data are mean ± SEM (n = 5 mice per group).