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(A) Molecular structures of ketone ester C6×2- R -1,3-BD and R- βHB. (B) Macronutrient composition of the ketone ester (KE) diet (20% C6×2- R -1,3-BD w/w) and the macro-controlled (CTL) diet. (C) Schematic of ketone ester diet paradigm. (D) Ratio of end-point (week 16, approximately 9.5 mo) to baseline body weights of WT and hTau+ mice fed with CTL or KE diets. (E-G) Representative immunofluorescent images (E) and quantification (F-G) of dorsal hippocampi of WT and hTau+ fed with CTL or KE diet, stained for MC1 (magenta) and DAPI (white). Quantification represents the average of 3+ sections per mouse, normalized to the hTau+ CTL group. DG, dentate gyrus. Scale bars: 200 μm. (H-I) Representative immunofluorescent images (H) and quantification (I) of dorsal hippocampi of WT and hTau+ fed with CTL or KE diet, stained with anti-NeuN (mature neurons). Quantification represents NeuN+ area within the hilus of bregma-matched sections (white outline), normalized to the WT CTL group. Scale bar: 200 μm. (J-L) Representative immunofluorescent images (J) and quantifications (K-L) of dorsal hippocampi of WT and hTau+ fed with CTL or KE diet, stained with anti-GFAP (green, reactive astrocytes) and anti-Iba1 (yellow, microglia). Quantification represents the average value of 3+ sections per mouse, normalized to the WT CTL group. Scale bars: 200 μm. Data are represented as mean ± SD. Each point represents one mouse. ** p < 0.01, *** p < 0.001, **** p < 0.0001 by Welch’s t-test (F-G) and Šídák’s multiple comparisons test (D, I, K, and L).
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(A) Molecular structures of ketone ester C6×2- R -1,3-BD and R- βHB. (B) Macronutrient composition of the ketone ester (KE) diet (20% C6×2- R -1,3-BD w/w) and the macro-controlled (CTL) diet. (C) Schematic of ketone ester diet paradigm. (D) Ratio of end-point (week 16, approximately 9.5 mo) to baseline body weights of WT and hTau+ mice fed with CTL or KE diets. (E-G) Representative immunofluorescent images (E) and quantification (F-G) of dorsal hippocampi of WT and hTau+ fed with CTL or KE diet, stained for MC1 (magenta) and DAPI (white). Quantification represents the average of 3+ sections per mouse, normalized to the hTau+ CTL group. DG, dentate gyrus. Scale bars: 200 μm. (H-I) Representative immunofluorescent images (H) and quantification (I) of dorsal hippocampi of WT and hTau+ fed with CTL or KE diet, stained with anti-NeuN (mature neurons). Quantification represents NeuN+ area within the hilus of bregma-matched sections (white outline), normalized to the WT CTL group. Scale bar: 200 μm. (J-L) Representative immunofluorescent images (J) and quantifications (K-L) of dorsal hippocampi of WT and hTau+ fed with CTL or KE diet, stained with anti-GFAP (green, reactive astrocytes) and anti-Iba1 (yellow, microglia). Quantification represents the average value of 3+ sections per mouse, normalized to the WT CTL group. Scale bars: 200 μm. Data are represented as mean ± SD. Each point represents one mouse. ** p < 0.01, *** p < 0.001, **** p < 0.0001 by Welch’s t-test (F-G) and Šídák’s multiple comparisons test (D, I, K, and L).

Journal: bioRxiv

Article Title: Ketone body β-hydroxybutyrate restores neuronal Tau proteostasis via ketolysis-independent mechanism

doi: 10.64898/2026.01.30.702936

Figure Lengend Snippet: (A) Molecular structures of ketone ester C6×2- R -1,3-BD and R- βHB. (B) Macronutrient composition of the ketone ester (KE) diet (20% C6×2- R -1,3-BD w/w) and the macro-controlled (CTL) diet. (C) Schematic of ketone ester diet paradigm. (D) Ratio of end-point (week 16, approximately 9.5 mo) to baseline body weights of WT and hTau+ mice fed with CTL or KE diets. (E-G) Representative immunofluorescent images (E) and quantification (F-G) of dorsal hippocampi of WT and hTau+ fed with CTL or KE diet, stained for MC1 (magenta) and DAPI (white). Quantification represents the average of 3+ sections per mouse, normalized to the hTau+ CTL group. DG, dentate gyrus. Scale bars: 200 μm. (H-I) Representative immunofluorescent images (H) and quantification (I) of dorsal hippocampi of WT and hTau+ fed with CTL or KE diet, stained with anti-NeuN (mature neurons). Quantification represents NeuN+ area within the hilus of bregma-matched sections (white outline), normalized to the WT CTL group. Scale bar: 200 μm. (J-L) Representative immunofluorescent images (J) and quantifications (K-L) of dorsal hippocampi of WT and hTau+ fed with CTL or KE diet, stained with anti-GFAP (green, reactive astrocytes) and anti-Iba1 (yellow, microglia). Quantification represents the average value of 3+ sections per mouse, normalized to the WT CTL group. Scale bars: 200 μm. Data are represented as mean ± SD. Each point represents one mouse. ** p < 0.01, *** p < 0.001, **** p < 0.0001 by Welch’s t-test (F-G) and Šídák’s multiple comparisons test (D, I, K, and L).

Article Snippet: Standard vivarium chow was PicoLab Rodent Diet 20 (LabDiet #5053).

Techniques: Staining