Poloxamer-188 Exacerbates Brain Amyloidosis, Presynaptic Dystrophies, and Pathogenic Microglial Activation in 5XFAD Mice

P188 administration in 5XFAD mice increased brain amyloid beta burden and exacerbated dystrophic neurite pathology.

• P188 was lethal at a concentration of 10mM but well tolerated at lower concentrations (1.2, 12, and 120μM).
• Administration of P188 may activate the γ-secretase pathway, leading to increased amyloid beta accumulation.
• Dystrophic neurite pathology worsened with P188 treatment, evident from higher levels of a lysosomal marker around amyloid deposits.
• Pathogenic microglial activation was also increased in P188-treated mice.
• Total tau levels decreased with P188 administration, while lysosomal enzyme cathepsin D and vesicular trafficking regulator SYT7 were dysregulated.

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