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Comment on “ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models”

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Science  24 May 2013:
Vol. 340, Issue 6135, pp. 924
DOI: 10.1126/science.1235809

Figures

  • Fig. 1

    Bexarotene restores cognitive function and decreases ISF Aβ in APP/E3 and APP/E4 mice. (A to C) APP/E3 and APP/E4 mice (7 months old) and matched nontransgenic littermates (E3 and E4) were treated with bexarotene or vehicle. N = 8 to 13 mice per group. RWM (7) was used to assess bexarotene effect on spatial learning deficits in APP/E3 (A) and APP/E4 mice (B). Analysis by two-way repeated-measures analysis of variance (ANOVA) shows a significant effect on treatment (P < 0.0001) and training (P < 0.001) in both APOE isoforms. Tukey’s post hoc test shows that bexarotene-treated APP mice were significantly different from vehicle-treated APP mice (P < 0.05 for both APOE isoforms) but not from their nontransgenic controls. (C) Novel object recognition test was performed on the same mice after RWM. Analysis by one-way ANOVA and Tukey’s post hoc test shows that bexarotene-treated APP mice were significantly different from vehicle-treated APP mice but not from their nontransgenic controls. (D) Bexarotene significantly decreases Aβ level in ISF. APP/E3 and APP/E4 mice (3.4 months old) were treated with bexarotene for 48 hours, and in vivo microdialysis was performed in the hippocampus as in (7). ISF Aβ40 and Aβ42 were determined by ELISA. Analysis by t test; N = 5 mice per group.

  • Fig. 2

    Bexarotene treatment does not affect amyloid deposition. After the behavior tests, the level of amyloid pathology was compared between treated and control mice within each genotype. (A) X-34 staining of compact fibrillar amyloid plaques in cortex and hippocampus (7). Representative pictures for X-34 (20X) are shown on the right. (B) Results of staining of brain sections with antibody to Aβ. For (A) and (B), N = 8 to 12 mice per group. Insoluble Aβ40 and Aβ42 in cortex (C) and hippocampus (D), and soluble Aβ in cortex (E) were measured by ELISA (N = 9 to 17 mice per group). (F) Bexarotene significantly decreased A11-positive oligomers (4). Intensity of the dots was quantified and normalized on the total protein measured on dot blots stained with coomassie blue. N = 7 to 9 mice. For all panels, analysis is by t test.

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