Olga Prikhodko, Kevin D. Rynearson, Travis Sekhon
Jan 13, 2020
Citations
0
Influential Citations
7
Citations
Quality indicators
Journal
Journal of Alzheimer's disease : JAD
Abstract
BACKGROUND In the amyloid hypothesis of Alzheimer's disease (AD), the dysregulation of amyloid-β protein (Aβ) production and clearance leads to amyloid deposits, tau tangles, neuronal loss, and cognitive dysfunction. Thus far, therapies targeting the enzymes responsible for Aβ production have been found ineffective or having significant side effects. OBJECTIVE To test whether a γ-secretase modulator, BPN-15606, is an effective disease-modifying or preventative treatment in the PSAPP mouse model of AD. METHODS We treated pre-plaque (3-month-old) and post-plaque (6-month-old) PSAPP AD transgenic mice for 3 months and examined behavioral, biochemical, and pathological end points. RESULTS BPN-15606 attenuated cognitive impairment and reduced amyloid plaque load, microgliosis, and astrogliosis associated with the AD phenotype of PSAPP mice when administered to pre-plaque (3-month-old) but was ineffective when administered to post-plaque (6-month-old) mice. No treatment-related toxicity was observed. CONCLUSION BPN-15606 appears efficacious when administered prior to significant pathology.