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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.