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- W2003443411 abstract "Alzheimer's disease (AD) is characterized by both amyloid β (Aβ) plaque deposition and intracellular neurofibrillary tangles accompanied by progressive cognitive decline. Aged transgenic Tg2576 mice show both plaque and well characterized cognitive impairments in several behavioral tasks. We have shown that NPT001 (filamentous bacteriophage M13) directly and potently dissociates fibrillary Aβ present in plaques and that it mediates tau aggregate clearance, indicating that NPT001 has broad amyloid-targeted activity. A variant of NPT001, NPT002, is in preclinical development for AD. This study was conducted to evaluate whether NPT002-induced Aβ clearance in aged Tg2576 mice is accompanied by cognitive improvement in tasks of spatial (Y Maze) and episodic (Novel Object Recognition, NOR) memory. In the present study, we administered bilaterally a single intra-hippocampal 2μL dose of NPT002 (2x10 11, 2x10 10, or 2x10 9 phage particles/injection) or PBS to 18-19 month old male Tg2576 mice and age-matched littermates. Animals were tested in a Y-Maze and in an NOR paradigm 5 and 6 days post-treatment, respectively. Animals were sacrificed 7 days post-treatment. Paraformaldehyde-fixed brains were serially sectioned with a vibratome and analyzed for Aβ load in the hippocampus and surrounding cortical areas by thioflavin S and anti-amyloid antibody staining (82E1); for neuro-inflammation by antibody staining for Iba1 and GFAP. Aged Tg2576 mice showed a performance deficit in the Y-Maze compared to aged-matched wild-type littermates. A single treatment with NPT002 produced a statistically significant dose-dependent amelioration of cognitive deficits in the Y-Maze, with NPT002 restoring the transgenic animals' spontaneous alternation activity to levels equal to that of their wild-type littermates. NPT002 also produce a dose-dependent improvement in the NOR test. All three NPT002 doses statistically reduced the levels of Aβ in the hippocampus and in the adjacent cortical tissue as measured with Aβ antibody and Thioflavin S staining. NPT002 represents a novel approach for reducing Aβ plaque. In an aged transgenic mouse model of AD (Tg2576), NPT002 was shown to both safely reduce Aβ load and ameliorate cognitive performance within one week following a single intra-hippocampal treatment, thus illustrating its potential as a promising treatment strategy for Alzheimer's disease." @default.
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- W2003443411 date "2012-07-01" @default.
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- W2003443411 title "P1‐342: NPT002 reduces beta‐amyloid aggregates and improves cognitive performance in aged TG2576 mice" @default.
- W2003443411 doi "https://doi.org/10.1016/j.jalz.2012.05.2028" @default.
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