For 12-month-old brain sections, the numbers of Aβ plaque in cortex and hippocampus were counted without the genotype

information. For 18- to 20-month-old mice, the area covered by Aβ was analyzed TSA HDAC manufacturer by ImageJ. The numbers of Thioflavin S-stained neuritic plaques were also analyzed by ImageJ. See Supplemental Experimental Procedures for details. Mice were injected once daily with BrdU (100 mg/kg, i.p.) for 3 consecutive days. Half of the mice in each group were sacrificed 1 day after the final injection of BrdU to identify proliferating neural progenitor cells (NPCs). The remaining mice were sacrificed 2 weeks after the final injection of BrdU to determine survival and neuronal differentiation of the newborn cells. See Supplemental Experimental Procedures for details. Data are presented as the mean ± SEM. Comparisons between two groups were performed with the independent-samples t test, and those among more than two groups were performed with

ANOVA followed by Tukey’s test. All analyses were performed with SPSS version 12.0. p value of <0.05 was considered statistically Epigenetics inhibitor significant. We thank Dr. Lin Wu for her scientific expertise and technical assistance in generating ADAM10 transgenic mice. We also thank Dr. Jorg Bartsch for providing ADAM10 prodomain antibody; Dr. Sam Sisodia for providing MoPrP.XhoI plasmid; Dr. Matthew Frosch for providing Tg2576 mice; Dr. Basavaraj Hooli and Dr. Can Zhang for helpful discussions; and William Wisdom for mouse tail genotyping. This study was supported by the Cure Alzheimer’s Fund, grants from the NIA, NIMH (R.E.T.), and the American Health Assistance Foundation (J.S.). “
“Tau

is a microtubule-associated protein that forms intracellular aggregates in several neurodegenerative diseases collectively termed tauopathies. These include Alzheimer’s disease (AD), progressive supranculear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal dementia (FTD) (Mandelkow and Mandelkow, 2012). Tau is a highly soluble and natively unfolded protein (Jeganathan et al., 2008) that binds and promotes the assembly ever of microtubules (Drechsel et al., 1992 and Witman et al., 1976). In tauopathies, tau accumulates in hyperphosphorylated neurofibrillary tangles (NFTs) that are visualized within dystrophic neurites and cell bodies (Mandelkow and Mandelkow, 2012). The amount of tau pathology correlates with progressive neuronal dysfunction, synaptic loss, and functional decline in humans and transgenic mouse models (Arriagada et al., 1992, Bancher et al., 1993, Polydoro et al., 2009 and Small and Duff, 2008). In human tauopathies, pathology progresses from one brain region to another in disease-specific patterns (Braak and Braak, 1997, Raj et al., 2012, Seeley et al., 2009 and Zhou et al., 2012), although the underlying mechanism is not yet clear.