Journal: Brain
Article Title: Tau, synapse loss and gliosis progress in an Alzheimer’s mouse model after amyloid-β immunotherapy
doi: 10.1093/brain/awae345
Figure Lengend Snippet: Amyloid–tau coexpression exacerbates tau tangles and axonal dystrophy in the APP/PS1xTau22 mouse model. ( A ) Amyloid-β (Aβ)-directed antibody reveals diffuse and dense-core Aβ plaques in the hippocampus and cortex of APP/PS1-derived mice. Plaque tissue coverage is equal between APP/PS1 and APP/PS1xTau22 mice in brain regions that accumulate fibrillar amyloid [hippocampus: t (18) = 0.32, P = 0.38; cortex: t (18) = 0.02, P = 0.16]. ( B ) Levels of non-fibrillar, soluble Aβ 1–42 species are also similar between genotypes, as measured by a human/rat-specific ELISA [ t (18) = 0.95, P = 0.18]. ( C ) AT8 immunolabelling marks extensive somatic and neuritic tau phosphorylation in CA1 regions and dentate gyrus of the hippocampus and cortex, and intensifies in amyloid-expressing animals [hippocampus: t (18) = 3.81, P = 0.0006; cortex: t (18) = 1.75, P = 0.049]. ( D and E ) Phospho-specific tau antibodies, AT100 and PHF1, label more advanced tau neurofibrillary structures in APP/PS1xTau22 mice compared with Tau22 littermates. [( D ) CA1: t (17) = 3.11, P = 0.003; cortex: t (12.6) = 2.40, P = 0.016; ( E ) CA1: t (17) = 2.49, P = 0.01; cortex: t (11.31) = 1.94, P = 0.04]. ( F ) Confocal micrographs of phospho-tau and axon-specific markers, AT8 and SMI312, respectively, show that the number of AT8 + puncta ( G ) and SMI312 + axonal swellings ( H ) are increased in the Aβ plaque core and corona when amyloid is coexpressed with pathological tau [plaque size measured: t (17) = 0.10, P = 0.46; AT8 + puncta/plaque: t (16) = 8.68, P < 0.0001; SMI312 + dystrophies/plaque: t (17) = 1.76, P = 0.048]. The plaque area measured is delineated by the dotted grey line. ns = not significant.
Article Snippet: Proteins were transferred to a nitrocellulose membrane using an iBlot transfer machine for 7 min at 25 V. Membranes were treated with LI-COR blocking buffer (LI-COR Biosciences) for 1 h at room temperature and incubated with primary antibodies against human tau (1:5000; Cat. No. A0024, DAKO) and human APP (1:5000 Cat. No. 29765, Cell Signaling), with GAPDH as a standardizing control (1:5000; Cat. No. 2118, Cell Signaling), overnight at 4°C.
Techniques: Derivative Assay, Enzyme-linked Immunosorbent Assay, Phospho-proteomics, Expressing
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![Amyloid–tau coexpression exacerbates tau tangles and axonal dystrophy in the <t>APP/PS1xTau22</t> mouse model. ( A ) Amyloid-β (Aβ)-directed antibody reveals diffuse and dense-core Aβ plaques in the hippocampus and cortex of APP/PS1-derived mice. Plaque tissue coverage is equal between APP/PS1 and APP/PS1xTau22 mice in brain regions that accumulate fibrillar amyloid [hippocampus: t (18) = 0.32, P = 0.38; cortex: t (18) = 0.02, P = 0.16]. ( B ) Levels of non-fibrillar, soluble Aβ 1–42 species are also similar between genotypes, as measured by a human/rat-specific ELISA [ t (18) = 0.95, P = 0.18]. ( C ) AT8 immunolabelling marks extensive somatic and neuritic tau phosphorylation in CA1 regions and dentate gyrus of the hippocampus and cortex, and intensifies in amyloid-expressing animals [hippocampus: t (18) = 3.81, P = 0.0006; cortex: t (18) = 1.75, P = 0.049]. ( D and E ) Phospho-specific <t>tau</t> <t>antibodies,</t> AT100 and PHF1, label more advanced tau neurofibrillary structures in APP/PS1xTau22 mice compared with Tau22 littermates. [( D ) CA1: t (17) = 3.11, P = 0.003; cortex: t (12.6) = 2.40, P = 0.016; ( E ) CA1: t (17) = 2.49, P = 0.01; cortex: t (11.31) = 1.94, P = 0.04]. ( F ) Confocal micrographs of phospho-tau and axon-specific markers, AT8 and SMI312, respectively, show that the number of AT8 + puncta ( G ) and SMI312 + axonal swellings ( H ) are increased in the Aβ plaque core and corona when amyloid is coexpressed with pathological tau [plaque size measured: t (17) = 0.10, P = 0.46; AT8 + puncta/plaque: t (16) = 8.68, P < 0.0001; SMI312 + dystrophies/plaque: t (17) = 1.76, P = 0.048]. The plaque area measured is delineated by the dotted grey line. ns = not significant.](https://pub-med-central-images-cdn.bioz.com/pub_med_central_ids_ending_with_7717/pmc11967717/pmc11967717__awae345f1.jpg)