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Cited by 141Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsGalectins and Cancer Biology

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Galectin-3 promotes Aβ oligomerization and Aβ toxicity in a mouse model of Alzheimer’s disease

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Tao, Chih-Chieh, Cheng, Kuang-Min, Ma, Yun-Li, Hsu, Wei-Lun, Chen, Yan-Chu, Fuh, Jong-Ling, Lee, Wei-Ju, Chao, Chih-Chang, Lee, Eminy H. Y.·2020·Cell Death & Differentiation
DOI 10.1038/s41418-019-0348-zPMC PMC7206130
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Abstract

Amyloid-β (Aβ) oligomers largely initiate the cascade underlying the pathology of Alzheimer’s disease (AD). Galectin-3 (Gal-3), which is a member of the galectin protein family, promotes inflammatory responses and enhances the homotypic aggregation of cancer cells. Here, we examined the role and action mechanism of Gal-3 in Aβ oligomerization and Aβ toxicities. Wild-type (WT) and Gal-3-knockout (KO) mice, APP/PS1;WT mice, APP/PS1;Gal-3 +/− mice and brain tissues from normal subjects and AD patients were used. We found that Aβ oligomerization is reduced in Gal-3 KO mice injected with Aβ, whereas overexpression of Gal-3 enhances Aβ oligomerization in the hippocampi of Aβ-injected mice. Gal-3 expression shows an age-dependent increase that parallels endogenous Aβ oligomerization in APP/PS1 mice. Moreover, Aβ oligomerization, Iba1 expression, GFAP expression and amyloid plaque accumulation are reduced in APP/PS1;Gal-3 +/− mice compared with APP/PS1;WT mice. APP/PS1;Gal-3 +/− mice also show better acquisition and retention performance compared to APP/PS1;WT mice. In studying the mechanism underlying Gal-3-promoted Aβ oligomerization, we found that Gal-3 primarily co-localizes with Iba1, and that microglia-secreted Gal-3 directly interacts with Aβ. Gal-3 also interacts with triggering receptor expressed on myeloid cells-2, which then mediates the ability of Gal-3 to activate microglia for further Gal-3 expression. Immunohistochemical analyses show that the distribution of Gal-3 overlaps with that of endogenous Aβ in APP/PS1 mice and partially overlaps with that of amyloid plaque. Moreover, the expression of the Aβ-degrading enzyme, neprilysin, is increased in Gal-3 KO mice and this is associated with enhanced integrin-mediated signaling. Consistently, Gal-3 expression is also increased in the frontal lobe of AD patients, in parallel with Aβ oligomerization. Because Gal-3 expression is dramatically increased as early as 3 months of age in APP/PS1 mice and anti-Aβ oligomerization is believed to protect against Aβ toxicity, Gal-3 could be considered a novel therapeutic target in efforts to combat AD.

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Fig. 1 Intra-hippocampal Aβ injection causes Aβ oligomerization in mice. a Naïve adult mice (3 months old) received a single injection of 1% NH4OH or Aβ (14 μg) to their hippocampal CA1 area. Fourteen days later, dorsal hippocampal tissues were dissected and subjected to Western blot analysis of Aβ oligomerization (left two lanes). In another group, Aβ (0.2 μg) was dissolved in 1% NH4OH and directly loaded to a gel for examination of Aβ oligomerization (far right lane). Aβ oligomerization is presented as high molecular weight (HMW) oligomers (>23 kDa) and low-molecular weight (LMW) oligomers (<23 kDa). b Quantification of the results for HMW and LMW Aβ oligomerization [n = 4 per group; t(1,6) = 8.91, P < 0.001 for HMW and t(1,6) = 4.0, P < 0.01 for LMW]. c Mice (3 months old) received injections of 1% NH4OH or Aβ (14 μg) to the CA1 area and were sacrificed at different time points (6 h, 48 h, 8 days, and 14 days) postinjection. Dissected dorsal hippocampal tissues were subjected to Western blot analysis of Aβ oligomerization. d Quantified results for HMW and LMW Aβ oligomerization [n = 4 per group; F(4,15) = 22.71, P < 0.001 for HMW and F(4,15) = 29.71, P < 0.001 for LMW]. Data are expressed as mean ± SEM. Statistical significances of various comparisons are shown in the figure. *P < 0.05, **P < 0.01, #P < 0.001 compared with the corresponding control group
Fig. 1 Intra-hippocampal Aβ injection causes Aβ oligomerization in mice. a Naïve adult mice (3 months old) received a single injection of 1% NH4OH or Aβ (14 μg) to their hippocampal CA1 area. Fourteen days later, dorsal hippocampal tissues were dissected and subjected to Western blot analysis of Aβ oligomerization (left two lanes). In another group, Aβ (0.2 μg) was dissolved in 1% NH4OH and directly loaded to a gel for examination of Aβ oligomerization (far right lane). Aβ oligomerization is presented as high molecular weight (HMW) oligomers (>23 kDa) and low-molecular weight (LMW) oligomers (<23 kDa). b Quantification of the results for HMW and LMW Aβ oligomerization [n = 4 per group; t(1,6) = 8.91, P < 0.001 for HMW and t(1,6) = 4.0, P < 0.01 for LMW]. c Mice (3 months old) received injections of 1% NH4OH or Aβ (14 μg) to the CA1 area and were sacrificed at different time points (6 h, 48 h, 8 days, and 14 days) postinjection. Dissected dorsal hippocampal tissues were subjected to Western blot analysis of Aβ oligomerization. d Quantified results for HMW and LMW Aβ oligomerization [n = 4 per group; F(4,15) = 22.71, P < 0.001 for HMW and F(4,15) = 29.71, P < 0.001 for LMW]. Data are expressed as mean ± SEM. Statistical significances of various comparisons are shown in the figure. *P < 0.05, **P < 0.01, #P < 0.001 compared with the corresponding control groupCC BY · PubMed Central
Fig. 2 Aβ oligomerization is reduced in Gal-3 KO mice injected with Aβ. a WT and Gal-3 KO mice (3 months old) were injected with 1% NH4OH or Aβ (5 μg) in the CA1 area. Animals were sacrificed 48 h after injection and dissected hippocampal tissues were subjected to Western blot analysis of Aβ oligomerization and Gal-3 expression. b Quantified results of HMW and LMW Aβ oligomerization [n = 4 per group; F(3,12) = 149.28, P < 0.001 for HMW; q = 26.22, P < 0.001 for the WT+NH4OH group versus the WT+Aβ group and q = 13.78, P < 0.001 for the WT+Aβ group versus the Gal-3 KO+Aβ group; F(3,12) = 48.02 and P < 0.001 for LMW; q = 14.31, P < 0.001 for the WT+NH4OH group versus the WT+Aβ group and q = 6.74, P < 0.001 for the WT+Aβ group versus the Gal-3 KO+Aβ group]. c Quantified results for Gal-3 expression in the same mouse groups [F(3,12) = 83.43, P < 0.001; q = 15.63, P < 0.001 for the WT+NH4OH group versus the WT+Aβ group]. d Mice (3 months old) received the following intra-hippocampal injections: NH4OH (1%) injection and Flag-vector plasmid (0.4 μg) transfection; Aβ (5 μg) injection and Flag-vector plasmid transfection; NH4OH injection and Flag-Gal-3 plasmid transfection; and Aβ injection and Flag-Gal-3 plasmid transfection. The two injections were given 2 h apart and animals were sacrificed 48 h after the injection of NH4OH or Aβ. Dissected hippocampal tissues were analyzed for Aβ oligomerization. Tissue lysates were also subjected to immunoprecipitation and immunoblotting with anti-Flag antibody to confirm transfection and expression of the plasmid. e Quantified results for HMW and LMW Aβ oligomerization [n = 4 per group; F(3,12) = 52.71, P < 0.001 for HMW; q = 9.09, P < 0.001 for the NH4OH+Flag-vector group versus the Aβ+Flag-vector group and q = 5.8, P < 0.01 for the Aβ+Flag-vector group versus the Aβ+Flag-Gal-3 group; F(3,12) = 72.63, P < 0.001 for LMW; q = 5.65, P < 0.01 for the NH4OH+Flag-vector group versus the Aβ+Flag-vector group and q = 12.38, P < 0.001 for the Aβ+Flag-vector group versus the Aβ+Flag-Gal-3 group]. Data are expressed as mean ± SEM. **P < 0.01, #P < 0.001
Fig. 2 Aβ oligomerization is reduced in Gal-3 KO mice injected with Aβ. a WT and Gal-3 KO mice (3 months old) were injected with 1% NH4OH or Aβ (5 μg) in the CA1 area. Animals were sacrificed 48 h after injection and dissected hippocampal tissues were subjected to Western blot analysis of Aβ oligomerization and Gal-3 expression. b Quantified results of HMW and LMW Aβ oligomerization [n = 4 per group; F(3,12) = 149.28, P < 0.001 for HMW; q = 26.22, P < 0.001 for the WT+NH4OH group versus the WT+Aβ group and q = 13.78, P < 0.001 for the WT+Aβ group versus the Gal-3 KO+Aβ group; F(3,12) = 48.02 and P < 0.001 for LMW; q = 14.31, P < 0.001 for the WT+NH4OH group versus the WT+Aβ group and q = 6.74, P < 0.001 for the WT+Aβ group versus the Gal-3 KO+Aβ group]. c Quantified results for Gal-3 expression in the same mouse groups [F(3,12) = 83.43, P < 0.001; q = 15.63, P < 0.001 for the WT+NH4OH group versus the WT+Aβ group]. d Mice (3 months old) received the following intra-hippocampal injections: NH4OH (1%) injection and Flag-vector plasmid (0.4 μg) transfection; Aβ (5 μg) injection and Flag-vector plasmid transfection; NH4OH injection and Flag-Gal-3 plasmid transfection; and Aβ injection and Flag-Gal-3 plasmid transfection. The two injections were given 2 h apart and animals were sacrificed 48 h after the injection of NH4OH or Aβ. Dissected hippocampal tissues were analyzed for Aβ oligomerization. Tissue lysates were also subjected to immunoprecipitation and immunoblotting with anti-Flag antibody to confirm transfection and expression of the plasmid. e Quantified results for HMW and LMW Aβ oligomerization [n = 4 per group; F(3,12) = 52.71, P < 0.001 for HMW; q = 9.09, P < 0.001 for the NH4OH+Flag-vector group versus the Aβ+Flag-vector group and q = 5.8, P < 0.01 for the Aβ+Flag-vector group versus the Aβ+Flag-Gal-3 group; F(3,12) = 72.63, P < 0.001 for LMW; q = 5.65, P < 0.01 for the NH4OH+Flag-vector group versus the Aβ+Flag-vector group and q = 12.38, P < 0.001 for the Aβ+Flag-vector group versus the Aβ+Flag-Gal-3 group]. Data are expressed as mean ± SEM. **P < 0.01, #P < 0.001CC BY · PubMed Central
Fig. 3 Aβ oligomerization and Gal-3 expression are age-dependently increased in APP/PS1 mice. a Wild-type (3 months old) and APP/PS1 mice of different ages (3, 5, 8, and 11 months) were sacrificed and dissected hippocampal tissues were subjected to Western blot analysis for endogenous Aβ oligomers. b Quantified results for HMW and LMW Aβ oligomerization [n = 4 per group; F(4,15) = 39.3, P < 0.001 for HMW and F(4,15) = 74.07, P < 0.001 for LMW]. Statistical significances for various comparisons are shown in the figure. c Western blot analysis showing the expression levels of Gal-3 and PIAS1 in hippocampal samples from the same batch of WT mice and APP/PS1 mice of different ages (n = 4 per group). d Quantified results for Gal-3 expression in WT and APP/PS1 mice [F(4,15) = 14.59, P < 0.001]. e Quantified results for PIAS1 expression in WT and APP/PS1 mice [F(4,15) = 5.86, P < 0.01] The letter “m” indicates month. Statistical significances of various comparisons are shown in the figure. Data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, #P < 0.001
Fig. 3 Aβ oligomerization and Gal-3 expression are age-dependently increased in APP/PS1 mice. a Wild-type (3 months old) and APP/PS1 mice of different ages (3, 5, 8, and 11 months) were sacrificed and dissected hippocampal tissues were subjected to Western blot analysis for endogenous Aβ oligomers. b Quantified results for HMW and LMW Aβ oligomerization [n = 4 per group; F(4,15) = 39.3, P < 0.001 for HMW and F(4,15) = 74.07, P < 0.001 for LMW]. Statistical significances for various comparisons are shown in the figure. c Western blot analysis showing the expression levels of Gal-3 and PIAS1 in hippocampal samples from the same batch of WT mice and APP/PS1 mice of different ages (n = 4 per group). d Quantified results for Gal-3 expression in WT and APP/PS1 mice [F(4,15) = 14.59, P < 0.001]. e Quantified results for PIAS1 expression in WT and APP/PS1 mice [F(4,15) = 5.86, P < 0.01] The letter “m” indicates month. Statistical significances of various comparisons are shown in the figure. Data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, #P < 0.001CC BY · PubMed Central
Fig. 4 Endogenous Aβ oligomerization, Gal-3 expression, Iba1 and GFAP distribution, and amyloid plaque are reduced in APP/PS1;Gal-3+/− mice. a Endogenous Aβ oligomerization was examined by Western blot analysis of samples obtained from 3-month-old WT;WT, APP/PS1;WT, WT;Gal-3−/− and APP/PS1;Gal-3+/− mice. b Quantified results for HMW and LMW Aβ oligomerization [n = 4 per group; F(3,12) = 110.36; P < 0.001 for HMW; q = 19.91, P < 0.001 for the WT;WT group versus the APP/PS1;WT group and q = 4.13, P = 0.01 for the APP/PS1;WT group versus the APP/PS1;Gal-3+/− group; F(3,12) = 77.72, P < 0.001 for LMW; q = 15.87, P < 0.001 for the WT;WT group versus the APP/PS1;WT group and q = 3.32, P < 0.05 for the APP/PS1;WT group versus the APP/PS1;Gal-3+/− group]. c Immunohistochemical analysis of Gal-3 and Iba1 and merged images for 7-month-old mice of the four genotypes. Scale bar, 25 μm. d Immunohistochemical analysis of Gal-3 and GFAP and merged image in 7-month-old mice of the four genotypes. Scale bar, 25 μm. e Immunohistochemical analysis showing the distribution of Gal-3 and ProteoStat in 11-month-old mice of the four genotypes. Scale bar, 200 μm. Data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, #P < 0.001
Fig. 4 Endogenous Aβ oligomerization, Gal-3 expression, Iba1 and GFAP distribution, and amyloid plaque are reduced in APP/PS1;Gal-3+/− mice. a Endogenous Aβ oligomerization was examined by Western blot analysis of samples obtained from 3-month-old WT;WT, APP/PS1;WT, WT;Gal-3−/− and APP/PS1;Gal-3+/− mice. b Quantified results for HMW and LMW Aβ oligomerization [n = 4 per group; F(3,12) = 110.36; P < 0.001 for HMW; q = 19.91, P < 0.001 for the WT;WT group versus the APP/PS1;WT group and q = 4.13, P = 0.01 for the APP/PS1;WT group versus the APP/PS1;Gal-3+/− group; F(3,12) = 77.72, P < 0.001 for LMW; q = 15.87, P < 0.001 for the WT;WT group versus the APP/PS1;WT group and q = 3.32, P < 0.05 for the APP/PS1;WT group versus the APP/PS1;Gal-3+/− group]. c Immunohistochemical analysis of Gal-3 and Iba1 and merged images for 7-month-old mice of the four genotypes. Scale bar, 25 μm. d Immunohistochemical analysis of Gal-3 and GFAP and merged image in 7-month-old mice of the four genotypes. Scale bar, 25 μm. e Immunohistochemical analysis showing the distribution of Gal-3 and ProteoStat in 11-month-old mice of the four genotypes. Scale bar, 200 μm. Data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, #P < 0.001CC BY · PubMed Central
Fig. 5 Endogenous Gal-3 expression is decreased but memory performance is improved in APP/PS1;Gal-3+/− mice. a Endogenous expression levels of Gal-3 and NEP were examined by Western blot analysis in 3-month-old WT;WT, APP/PS1;WT, WT;Gal-3−/− and APP/PS1;Gal-3+/− mice. b Quantified results for Gal-3 and NEP expression [n = 4 per group; for Gal-3, F(3,12) = 53.47, P < 0.001; q = 10.43, P < 0.001 for the WT;WT group versus the APP/PS1;WT group; q = 6.46, P < 0.001 for the APP/PS1;WT group versus the APP/PS1;Gal-3+/− group and q = 3.98, P < 0.05 for the WT;WT group versus the APP/PS1;Gal-3+/− group; for NEP, F(3,12) = 27.76, P < 0.001; q = 12.04, P < 0.001 for the WT;WT group versus the APP/PS1;WT group; q = 9.72, P < 0.001 for the WT;WT group versus the WT;Gal-3−/− group and q = 6.29, P < 0.01 for the WT;WT group versus the APP/PS1;Gal-3+/− group]. c Acquisition performance obtained by assessing the water maze learning of 8-month-old mice of the four genotypes [n = 7 per group; F(3,24) = 28.72, P < 0.001; q = 9.33, P < 0.001 for the APP/PS1;WT group versus the WT;WT group and q = 3.59, P < 0.05 for the APP/PS1;Gal-3+/− group versus the APP/PS1;WT group]. d Retention performance of the same mice described in (c) [n = 7 per group; F(3,24) = 4.76, P < 0.01; q = 3.94, P < 0.05 for the APP/PS1;WT group versus the WT;WT group; q = 3.25, P < 0.05 for the APP/PS1;Gal-3+/− group versus the APP/PS1;WT group for the target quadrant]. Representative swim patterns from each group are also shown (upper panel). Data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, #P < 0.001
Fig. 5 Endogenous Gal-3 expression is decreased but memory performance is improved in APP/PS1;Gal-3+/− mice. a Endogenous expression levels of Gal-3 and NEP were examined by Western blot analysis in 3-month-old WT;WT, APP/PS1;WT, WT;Gal-3−/− and APP/PS1;Gal-3+/− mice. b Quantified results for Gal-3 and NEP expression [n = 4 per group; for Gal-3, F(3,12) = 53.47, P < 0.001; q = 10.43, P < 0.001 for the WT;WT group versus the APP/PS1;WT group; q = 6.46, P < 0.001 for the APP/PS1;WT group versus the APP/PS1;Gal-3+/− group and q = 3.98, P < 0.05 for the WT;WT group versus the APP/PS1;Gal-3+/− group; for NEP, F(3,12) = 27.76, P < 0.001; q = 12.04, P < 0.001 for the WT;WT group versus the APP/PS1;WT group; q = 9.72, P < 0.001 for the WT;WT group versus the WT;Gal-3−/− group and q = 6.29, P < 0.01 for the WT;WT group versus the APP/PS1;Gal-3+/− group]. c Acquisition performance obtained by assessing the water maze learning of 8-month-old mice of the four genotypes [n = 7 per group; F(3,24) = 28.72, P < 0.001; q = 9.33, P < 0.001 for the APP/PS1;WT group versus the WT;WT group and q = 3.59, P < 0.05 for the APP/PS1;Gal-3+/− group versus the APP/PS1;WT group]. d Retention performance of the same mice described in (c) [n = 7 per group; F(3,24) = 4.76, P < 0.01; q = 3.94, P < 0.05 for the APP/PS1;WT group versus the WT;WT group; q = 3.25, P < 0.05 for the APP/PS1;Gal-3+/− group versus the APP/PS1;WT group for the target quadrant]. Representative swim patterns from each group are also shown (upper panel). Data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, #P < 0.001CC BY · PubMed Central
Fig. 6 Galectin-3 associates with Aβ and interacts with Aβ. a Immunohistochemical analysis showing the distributions of endogenous Gal-3 and Aβ in hippocampal samples of WT (left panel) and APP/PS1 (right panel) mice at 11 months of age. Scale bar, 200 μm. b Co-IP experiment showing preferential association of Gal-3 with endogenous Aβ monomers in 8-month-old APP/PS1 mice. Experiments were performed in duplicate. c Different amounts of recombinant human Gal-3 protein (0.25, 0.5, 1, and 2 μg) were added to a solution containing Aβ42 peptide (15 μg), the mixture was subjected to a thioflavin-T assay, and fluorescence was measured hourly at different time points. The fluorescence plateaued at the 7-h time point. Experiments were performed in triplicate. The abbreviation “rh” indicates “recombinant human”. Data are expressed as mean ± SEM
Fig. 6 Galectin-3 associates with Aβ and interacts with Aβ. a Immunohistochemical analysis showing the distributions of endogenous Gal-3 and Aβ in hippocampal samples of WT (left panel) and APP/PS1 (right panel) mice at 11 months of age. Scale bar, 200 μm. b Co-IP experiment showing preferential association of Gal-3 with endogenous Aβ monomers in 8-month-old APP/PS1 mice. Experiments were performed in duplicate. c Different amounts of recombinant human Gal-3 protein (0.25, 0.5, 1, and 2 μg) were added to a solution containing Aβ42 peptide (15 μg), the mixture was subjected to a thioflavin-T assay, and fluorescence was measured hourly at different time points. The fluorescence plateaued at the 7-h time point. Experiments were performed in triplicate. The abbreviation “rh” indicates “recombinant human”. Data are expressed as mean ± SEMCC BY · PubMed Central
Fig. 7 Neprilysin (NEP) expression is increased and integrin signaling is enhanced in Gal-3 KO mice. a Dissected hippocampi of naïve WT and Gal-3 KO mice (3-month-old) were subjected to various Western blot assays. Representative gel patterns obtained for NEP, IDE, TTR, and Gal-3 are shown. b Quantified results for NEP expression [t(1,8) = 8.61, P < 0.001; left panel], IDE expression [t(1,8) = 0.72, P > 0.05; middle panel] and TTR expression [t(1,8) = 1.32, P > 0.05; right panel]. c Representative gel patterns obtained for pFAK, FAK, pCREB, and CREB, and their quantified results [t(1,8) = 11.14, P < 0.001 for pFAK/FAK; t(1,8) = 0.57, P > 0.05 for FAK/Actin; t(1,8) = 6.72, P < 0.001 for pCREB/CREB and t(1,8) = 0.67, P > 0.05 for CREB/Actin]. d ChIP assay examining the binding of endogenous CREB to the NEP promoter in WT and Gal-3 KO mice, and the quantified results [t(1,8) = 9.06, P < 0.001]. Data are expressed as mean ± SEM. #P < 0.001
Fig. 7 Neprilysin (NEP) expression is increased and integrin signaling is enhanced in Gal-3 KO mice. a Dissected hippocampi of naïve WT and Gal-3 KO mice (3-month-old) were subjected to various Western blot assays. Representative gel patterns obtained for NEP, IDE, TTR, and Gal-3 are shown. b Quantified results for NEP expression [t(1,8) = 8.61, P < 0.001; left panel], IDE expression [t(1,8) = 0.72, P > 0.05; middle panel] and TTR expression [t(1,8) = 1.32, P > 0.05; right panel]. c Representative gel patterns obtained for pFAK, FAK, pCREB, and CREB, and their quantified results [t(1,8) = 11.14, P < 0.001 for pFAK/FAK; t(1,8) = 0.57, P > 0.05 for FAK/Actin; t(1,8) = 6.72, P < 0.001 for pCREB/CREB and t(1,8) = 0.67, P > 0.05 for CREB/Actin]. d ChIP assay examining the binding of endogenous CREB to the NEP promoter in WT and Gal-3 KO mice, and the quantified results [t(1,8) = 9.06, P < 0.001]. Data are expressed as mean ± SEM. #P < 0.001CC BY · PubMed Central
Fig. 8 Aβ oligomerization and Gal-3 expression are increased in AD patients. The frontal lobe lysates of normal subjects and AD patients were subjected to Western blot analysis for Aβ oligomerization and the expression of Gal-3 and Gal-1 (n = 4 per group). b–d Quantified results for (b) HMW [t(1,6) = 9.72, P < 0.001] and LMW [t(1,6) = 7.21, P < 0.001] Aβ oligomerization, c Gal-3 expression [t(1,6) = 4.92, P < 0.01] and d Gal-1 expression [t(1,6) = 0.43, P > 0.05]. e Immunohistochemical analysis showing the distributions of Gal-3 and ProteoStat staining in normal subjects and AD patients (n = 3 per group). Scale bar, 25 μm. DAPI was used to stain nuclei. Data are expressed as mean ± SEM. **P < 0.01, #P < 0.001
Fig. 8 Aβ oligomerization and Gal-3 expression are increased in AD patients. The frontal lobe lysates of normal subjects and AD patients were subjected to Western blot analysis for Aβ oligomerization and the expression of Gal-3 and Gal-1 (n = 4 per group). b–d Quantified results for (b) HMW [t(1,6) = 9.72, P < 0.001] and LMW [t(1,6) = 7.21, P < 0.001] Aβ oligomerization, c Gal-3 expression [t(1,6) = 4.92, P < 0.01] and d Gal-1 expression [t(1,6) = 0.43, P > 0.05]. e Immunohistochemical analysis showing the distributions of Gal-3 and ProteoStat staining in normal subjects and AD patients (n = 3 per group). Scale bar, 25 μm. DAPI was used to stain nuclei. Data are expressed as mean ± SEM. **P < 0.01, #P < 0.001CC BY · PubMed Central

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Authors
Tao, C.-C., Cheng, K.-M., Ma, Y.-L., Hsu, W.-L., Chen, Y.-C., Fuh, J.-L., Lee, W.-J., Chao, C.-C., & Lee, E. H. Y.
Affiliations
  • Institute of Biomedical Sciences, Academia Sinica (TW)
  • Taipei Veterans General Hospital (TW)
  • Taichung Veterans General Hospital (TW)
  • National Chengchi University (TW)
Corresponding author
Lee, Eminy H. Y.
ORCID
Venue
Cell Death & Differentiation
Publisher
Springer Science and Business Media LLC
Published
2019-05-24
Volume
27
Issue
1
Pages
192-209
ISSN
  • 1350-9047 (ISSN-L)
  • 1476-5403
DOI
10.1038/s41418-019-0348-z
PMC
PMC7206130
OpenAlex
W2944988109
Cited by
138
References
51
Citations by year
2026: 12 · 2025: 21 · 2024: 32 · 2023: 13 · 2022: 30 · 2021: 20 · 2020: 9 · 2019: 1
FWCI
10.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Differentiation (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Ministry of Science and Technology, Taiwan (MOST 106-2320-B-001-005-MY3)
  • Institute of Biomedical Sciences, Academia Sinica, Taiwan
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Galectins and Cancer Biology
Keywords
amyloid-beta oligomers, Alzheimer's disease, amyloid-beta toxicity, microglia, TREM2, neprilysin, APP/PS1 mice, amyloid plaques, hippocampus, integrin signaling, galectin-3 knockout mice, cognitive impairment, therapeutic target
MeSH terms
Age Factors, Alzheimer Disease, Animals, Blood Proteins, Calcium-Binding Proteins, Disease Models, Animal, Female, Glial Fibrillary Acidic Protein, Hippocampus, Male, Memory, Mice, Transgenic, Microfilament Proteins, Peptide Fragments, Neprilysin, Signal Transduction, Integrins, Amyloid beta-Peptides, Rats, Sprague-Dawley, Mice, Knockout, Galectins, Galectin 3, Mice, Plaque, Amyloid, Amyloidogenic Proteins

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