Qi Zhang

TL;DR: In vivo studies show that inhibition of γ-secretase has the expected benefit of reducing Aβ in a murine model of Alzheimer disease but has potentially undesirable biological effects as well, most likely because of the inhibition of Notch processing.

TL;DR: A number of APP genotype-related changes in the fine-tuning of the CA1 area circuitry, some of which are likely to contribute to the pathology-dependent effects on LTP observed in CRND8 mice, are suggested.

TL;DR: Compared to their Non-Tg littermates, Tg CRND8 mice demonstrate cognitive impairments that progressed with age and seemed to coincide with the onset of beta-amyloid plaque deposition.

TL;DR: Based on a lead compound identified from the patent literature, patentably novel BACE-1 inhibitors are developed by introducing a cyclic amine scaffold as embodied by 1a and 1b.

TL;DR: The present studies demonstrate that the 3- to 5-fold therapeutic window for LY411,575 can be exploited to obtain reduction in Aβ levels without induction of intestinal side effects, that intermittent treatment could be used to mitigate side results, and that a 6-day dosing paradigm can be use to rapidly determine the therapeutic window of novel γ-secretase inhibitors.