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Table 1 Comparison between the main pathology markers in Tg2576 mice chronically treated either with a γ-secretase inhibitor (DAPT) and a mixed γ-secretase modulator with anti-inflammatory properties (CHF5074)

From: Multi-target action of the novel anti-Alzheimer compound CHF5074: in vivo study of long term treatment in Tg2576 mice

Task/marker DAPT CHF5074
Novel object recognition test (recognition index) unchanged restored at wild-type level at 375ppm
amyloid plaque burden unchanged reduced
oligomers   
plasma Aβ42 increased increased at 375ppm
intraneuronal Aβ reduced reduced
microglia activation (Iba1-IR) unchanged reduced
Dendritic spine density (CA1/2 pyramidal neurons) restored at wild-type level increased at 375ppm, compared to Tg2576 vehicle
Aberrant cell cycle events (cyclinA-IR neurons) lightly reduced (−28%) strongly reduced (−63%)
  1. Treatments were started in 6month old rats and protracted for 13 months. Behavioral test was then carried out in 18month old animals, and all post-mortem observation in 19month old animals.