Journal: Molecular Neurodegeneration

Article Title: Tau oligomers modulate synapse fate by eliciting progressive bipartite synapse dysregulation and synapse loss

doi: 10.1186/s13024-026-00928-2

Figure Lengend Snippet: Mapping the longer-term postsynaptic proteome dynamics following acute tau oligomer exposure shows an upregulation of postsynaptic disease-related proteins. A Workflow of treatment of human neurons with tau oligomers followed by proximity labeling of postsynaptic proteins 24 h later. B SynGO cellular component analyses of 1,436 biotinylated proteins identified by mass spectrometry from untreated and tau oligomer-treated human neurons. Size of circles denotes protein count, colors denote p-values and protein ratio denotes protein count over total number of proteins. C SynGO analysis showed 300 annotated postsynaptic proteins including the proteins classified in child terms. D Schematic diagram of key biotinylated postsynaptic proteins identified in human neurons. E Venn diagram of the 1,436 biotinylated proteins detected from untreated neurons and tau oligomer-exposed human neurons highlighting upregulated (red) and downregulated (blue) proteins at 24 h after tau oligomer exposure compared to untreated controls ( n = 6 cultures/group; p < 0.05 with absolute average log 2 ratio > 0.25). F Protein interaction network based on STRING database analysis of the 57 upregulated proteins in tau oligomer-treated neurons. Single proteins are not shown. Colors depict Reactome pathway categories. G Representative confocal images of GSK3β (red), PSD-95 (green) and MAP2 (blue) immunostaining in human neurons exposed to tau oligomers for 30 min and fixed 24 h later. Scale bar: 5 μm. H Quantification of postsynaptic GSK3β immunolabeling intensity that colocalized with PSD-95 in human neurons treated with tau oligomers for 30 min and fixed after 24 h. I Schematic diagram of upregulated biotinylated proteins in tau oligomer-exposed neurons, which were also identified in the human postsynaptic proteome, showing postsynaptic cellular classifications. Size of circles denotes fold change and colors denote p-values

Article Snippet: Primary antibodies used for western blot and immunocytochemistry were: Tau5 (AB_80579, Abcam), Streptavin HRP (S911, Invitrogen), GAPDH (MAB374, Sigma), Rabbit flag (F7425, Sigma), Mouse flag (F3165, Sigma), PSD-95 (MA1046, ThermoFisher), GluA2/3 (AB1506, MilliporeSigma), Cy3 Streptavidin (AB_2337244, Jackson Immunoresearch), Mouse vGluT1 (MAB5502, MilliporeSigma), Guinea Pig vGluT1 (AB5905, MilliporeSigma), GluA1 (ABN241, MilliporeSigma), GluN1 (114 011, SynapticSystems), Synapsin (5297 S, Cell Signaling), Rabbit MAP2 (4542 S, Cell Signaling), Chicken MAP2 (NB300 213, Novus Biologicals), NeuN ( AB177487 , Abcam), GFAP ( PA110004 , Invitrogen), Rabbit GSK3β (ab32391, Abcam), and MYO5A ( AB244249 , Abcam).

Techniques: Labeling, Mass Spectrometry, Immunostaining, Immunolabeling

Journal: Molecular Neurodegeneration

Article Title: Tau oligomers modulate synapse fate by eliciting progressive bipartite synapse dysregulation and synapse loss

doi: 10.1186/s13024-026-00928-2

Figure Lengend Snippet: A brief tau oligomer exposure causes a prolonged degenerative effect in human neurons. A Workflow indicating that the 30-min treatment with tau oligomers was followed by different intervals of time (30 min, 1 h, 24 h, 7 days, or 14 days) before the fixation of human neuron cultures for experiments. B Confocal images of human neurons treated with oligomerized tau conjugated with Fluorescein-5-isothiocyanate (tau-FITC) (green) showed colocalization (white arrowheads) of tau-FITC with Synapsin (blue) and PSD-95 (red). Scale bar: 5 μm. C Representative confocal images of human neurons at 30 min, 1 h and 24 h after the 30 min exposure with oligomerized tau-FITC as described in A . Scale bar: 5 μm. D Quantification of the integrated intensity of tau-FITC fluorescence at synapses in human neurons that were treated with oligomerized tau-FITC for 30 min and fixed at different time points A ( n = 12 images/group; ** p < 0.01, *** p < 0.001, one-way ANOVA, Bonferroni post hoc analyses). E-H Representative images of NeuN immunolabeling, as a neuronal marker, in vehicle-treated control neurons and in neurons at either ( E ) 7 or ( G ) 14 days after the 30-min exposure to tau oligomers. ( F , H ) The density of NeuN-positive cells in the cultures was calculated and compared with or without tau oligomer exposure ( n = 12 images/group; no significant difference, Unpaired Student’s t -test). Scale bar: 100 mm. I-L Representative confocal images of MAP2 immunostaining in neurons at ( I ) 7 or ( K ) 14 days after the 30-min tau oligomer treatment and in neurons treated with vehicle control. Scale bars: 20 μm. The intensity of MAP2 immunolabeling in dendrites of human neurons was quantified at ( J ) 7 days ( n = 12 images/group; no significant difference, Unpaired Student’s t -test) and ( L ) 14 days ( n = 12 images/group; *** p < 0.001, Unpaired Student’s t -test) post-oligomer exposure. Values are given as means ± SEM

Article Snippet: Primary antibodies used for western blot and immunocytochemistry were: Tau5 (AB_80579, Abcam), Streptavin HRP (S911, Invitrogen), GAPDH (MAB374, Sigma), Rabbit flag (F7425, Sigma), Mouse flag (F3165, Sigma), PSD-95 (MA1046, ThermoFisher), GluA2/3 (AB1506, MilliporeSigma), Cy3 Streptavidin (AB_2337244, Jackson Immunoresearch), Mouse vGluT1 (MAB5502, MilliporeSigma), Guinea Pig vGluT1 (AB5905, MilliporeSigma), GluA1 (ABN241, MilliporeSigma), GluN1 (114 011, SynapticSystems), Synapsin (5297 S, Cell Signaling), Rabbit MAP2 (4542 S, Cell Signaling), Chicken MAP2 (NB300 213, Novus Biologicals), NeuN ( AB177487 , Abcam), GFAP ( PA110004 , Invitrogen), Rabbit GSK3β (ab32391, Abcam), and MYO5A ( AB244249 , Abcam).

Techniques: Fluorescence, Immunolabeling, Marker, Control, Immunostaining