Figure 4.

Neuronal TFEB transduction reduces amyloid plaque load in APP/PS1 mice. A, Schematic representation of specific antibodies used in ELISA. B, C, Aβ40 and Aβ42 levels in dissected hippocampal tissues from AAV8-CMV-FLAG-TFEB (TFEB) and AAV8-CMV-GFP (GFP)-transduced mice (10 months of age). Tissue was homogenized first in PBS (soluble levels, B), then in 5 mm guanidine (insoluble levels, C) quantified with ELISA assay. HJ2 and HJ7.4 antibodies were used for capture Aβ40 and Aβ42, respectively, and HJ5.1 antibody was used for detection. Total Aβ levels were also measured with a combination of HJ5.1 antibody for capture and HJ3.5 antibody for detection, as indicated in the schematic. N = 8 mice per group; *p < 0.05, **p < 0.01. D, Representative X-34-stained images from APP/PS1 mice treated as in A. The area of the hippocampus is outlined with a dotted line. E, F, Quantification of X-34-stained plaque burden in the hippocampus (HPC) in mice treated as in A (E) and plaque burden stratified by sex (F). N = 14 (6 male and 8 female) mice per group;*p < 0.05, **p < 0.01. G, Representative Aβ-immunostained images from mice treated as in B. H, I, Quantification of Aβ-stained plaque burden in the hippocampus in mice treated as in A (H) and plaque burden stratified by sex (I). N = 14 (6 male and 8 female) mice per group; *p < 0.05, **p < 0.01. HPC, Hippocampus; CTX, cortex.