Journal: Molecular Neurodegeneration

Article Title: Islet amyloid polypeptide cross-seeds tau and drives the neurofibrillary pathology in Alzheimer’s disease

doi: 10.1186/s13024-022-00518-y

Figure Lengend Snippet: IAPP-Tau PFFs promote the propagation of tau pathology in vivo. a, b Representative images of AT8 p-tau pathology in tissue sections (anterior hippocampal level) from the hippocampus, dentate gyrus, retrosplenial cortex, and entorhinal cortex of tau P301S mice 1 month ( a ) and 3 months ( b ) after the injection of PBS, tau PFFs or IAPP-tau PFFs. Scale bar, 200 μm in ( a ) and ( b ) upper panel, 50 μm in ( a ) and ( b ) lower panels. c-j Quantification of p-tau pathology of ipsilateral and contralateral sides in the hippocampus ( c, d ), dentate gyrus ( e, f ), entorhinal cortex ( g, h ), and retrosplenial cortex ( i, j ). n = 4 mice per group. Data are presented as means ± SEM. One-way ANOVA followed by Tukey’s post hoc test. * P < 0.05, ** P < 0.01, ***P < 0.001, n.s. not significant

Article Snippet: Tau P301S transgenic mice (line PS19) and tau knockout mice were from Jackson Laboratory (stock number: 008169 and 007251, respectively).

Techniques: In Vivo, Injection

Journal: Molecular Neurodegeneration

Article Title: Islet amyloid polypeptide cross-seeds tau and drives the neurofibrillary pathology in Alzheimer’s disease

doi: 10.1186/s13024-022-00518-y

Figure Lengend Snippet: IAPP-tau PFFs induce cognitive impairment and synaptic dysfunction in vivo. Three-month-old male mice were injected with PBS, tau PFFs or IAPP-tau PFFs, respectively. The mice were sacrificed three months after PFF injection. a Spatial memory was assessed by the Morris water maze test. Shown are the distance traveled to the platform by mice injected with PBS, Tau PFFs, or IAPP-Tau PFFs. b Integrated time traveled in Morris water maze test. AUC, area under the curve. c Average swim speed of mice in three groups. d Probe trial results. n = 9 mice in PBS group, n = 12 mice in Tau PFFs group, n = 7 mice in IAPP-tau PFFs group. e Time spent in the novel arm in the Y-maze test. n = 7 mice per group. f Long-term potentiation (LTP) of fEPSPs was induced by 3 × TBS (4 pulses at 100 Hz, repeated three times with a 200-ms interval). The magnitude of LTP and synaptic transmission was assessed by input/output (I/O). g Representative fEPSPs of hippocampal slices prepared from mice in three groups. n = 3 mice per group. h Electron microscopy of synapses (top) and magnification (below). Scale bar, 1 μm in the top panel, 200 nm in the lower panel. i The number of synaptic clefts. j Postsynaptic density. k Length of the active zone. l Width of synaptic clefts. n = 10–15 slices per group. m, n Golgi staining of dendritic spines of hippocampal slides. Scale bar, 20 μm. n = 10 slices per group. o Western blot analysis of synaptic markers in the ipsilateral hippocampus of tau P301S mice. p-r Quantification for synaptophysin ( p ), synapsin I ( q ), and PSD95 ( r ), n = 3 mice per group. Data are presented as means ± SEM. One-way ANOVA followed by Tukey’s post hoc test. *P < 0.05, **P < 0.01, *** P < 0.001. n.s. not significant

Article Snippet: Tau P301S transgenic mice (line PS19) and tau knockout mice were from Jackson Laboratory (stock number: 008169 and 007251, respectively).

Techniques: In Vivo, Injection, Transmission Assay, Electron Microscopy, Staining, Western Blot

Journal: Molecular Neurodegeneration

Article Title: Islet amyloid polypeptide cross-seeds tau and drives the neurofibrillary pathology in Alzheimer’s disease

doi: 10.1186/s13024-022-00518-y

Figure Lengend Snippet: IAPP deposits in the brain of AD patients. a Representative images of IAPP deposition in the hippocampal sections of AD patients and age-matched controls. b Quantification of the percentage of IAPP-positive cells. Scale bars, 50 μm. Bars represent means ± SEM. Unpaired Student’s t- test. n = 10 slides from 10 AD patients and 10 slides from 10 control subjects. *** P < 0.001. c Western bolt assay detects the presence of IAPP in the formic acid fraction from AD brains. n = 3 AD patients and 3 controls. d Concentrations of IAPP in the CSF of AD patients ( n = 11) and healthy controls ( n = 22). Bars represent means ± SEM. Unpaired Student’s t -test, ***P < 0.001. e Co-immunostainings of IAPP and phosphorylated tau (p-tau) in brain sections of AD patients. n = 10 AD patients and 10 controls. Scale bars, 20 μm. f Co-immunoprecipitation showing the interaction between IAPP and p-tau in AD human brains. n = 3 AD patients and 3 controls. g RT-PCR analysis found no IAPP mRNA expression in both AD and control brains. n = 4 AD patients and 4 controls. (h, i) Uptake of intravenously injected pure IAPP PFFs by neurons ( g ) and microglia ( h ) in tau P301S mice. Scale bars, 20 μm

Article Snippet: Tau P301S transgenic mice (line PS19) and tau knockout mice were from Jackson Laboratory (stock number: 008169 and 007251, respectively).

Techniques: Control, Western Blot, Immunoprecipitation, Reverse Transcription Polymerase Chain Reaction, Expressing, Injection

Journal: Current Opinion in Pharmacology

Article Title: The pleiotropic roles of autophagy in Alzheimer's disease: From pathophysiology to therapy

doi: 10.1016/j.coph.2021.07.011

Figure Lengend Snippet: Molecules tested for amelioration of AD pathology through modulation of autophagy.

Article Snippet: Treatment with Apt-1 also restored tau proteostasis in the PS19 mouse model [ ].

Techniques: Transgenic Assay, Activation Assay, Ubiquitin Proteomics, Translocation Assay