This database contains 6 studies, archived under the term: "amyloid precursor protein secretases"
Amyloid-β(1-15/16) as a marker for γ-secretase inhibition in Alzheimer’s disease
Portelius, Erik,
Zetterberg, Henrik,
Dean, Robert A.,
Marcil, Alexandre,
Bourgeois, Philippe,
Nutu, Magdalena,
Andreasson, Ulf,
Siemers, Eric,
Mawuenyega, Kwasi G.,
Sigurdson, Wendy C.,
May, Patrick C.,
Paul, Steven M.,
Holtzman, David M.,
Blennow, Kaj,
Bateman, Randall J.
Amyloid-β (Aβ) producing enzymes are key targets for disease-modifying Alzheimer’s disease (AD) therapies since Aβ trafficking is at the core of AD pathogenesis. Development of such drugs might benefit from the identification of markers indicating in vivo drug effects in the central nervous system. We have previously shown that Aβ(1-15) is produced by concerted β-and […]
A placebo-controlled, multiple ascending dose study to evaluate the safety, pharmacokinetics and pharmacodynamics of avagacestat (BMS-708163) in healthy young and elderly subjects
Dockens, Randy,
Wang, Jun-Sheng,
Castaneda, Lorna,
Sverdlov, Oleksandr,
Huang, Shu-Pang,
Slemmon, Randy,
Gu, Huidong,
Wong, Oi,
Li, Hewei,
Berman, Robert M.,
Smith, Christina,
Albright, Charles F.,
Tong, Gary
Background and Objectives: Avagacestat is an orally active γ-secretase inhibitor that selectively inhibits amyloid β (Aβ) synthesis in cell culture and animal models. The objective of the current study was to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of multiple doses of avagacestat over 28 days in healthy young men and elderly men and women […]
Increased CSF APPs-α levels in patients with Alzheimer disease treated with acitretin
Endres, Kristina,
Fahrenholz, Falk,
Lotz, Johannes,
Hiemke, Christoph,
Teipel, Stefan,
Lieb, Klaus,
Tüscher, Oliver,
Fellgiebel, Andreas
Objective: We investigated induction of α-secretase A disintegrin and metalloprotease 10 (ADAM10) by the synthetic retinoid acitretin (Neotigason; Actavis, München-Riem, Germany) in patients with mild to moderate Alzheimer disease (AD) via measurement of CSF content of α-secretase-derived amyloid precursor protein (APPs-α).; Methods: Twenty-one patients clinically diagnosed with mild to moderate AD received acitretin (30 mg […]
Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial
Green, Robert C.,
Schneider, Lon S.,
Amato, David A.,
Beelen, Andrew P.,
Wilcock, Gordon,
Swabb, Edward A.,
Zavitz, Kenton H.
Context: Amyloid-beta peptide (Abeta(42)) has been implicated in the pathogenesis of Alzheimer disease (AD). Tarenflurbil, a selective Abeta(42)-lowering agent, demonstrated encouraging results on cognitive and functional outcomes among mildly affected patients in an earlier phase 2 trial.; Objective: To determine the efficacy, safety, and tolerability of tarenflurbil.; Design, Setting, and Patients: A multicenter, randomized, double-blind, […]
A phase 3 trial of semagacestat for treatment of Alzheimer’s disease
Doody, Rachelle S.,
Raman, Rema,
Farlow, Martin,
Iwatsubo, Takeshi,
Vellas, Bruno,
Joffe, Steven,
Kieburtz, Karl,
He, Feng,
Sun, Xiaoying,
Thomas, Ronald G.,
Aisen, Paul S,
Siemers, Eric,
Sethuraman, Gopalan,
Mohs, Richard
Background: Alzheimer’s disease is characterized by the presence of cortical amyloid-beta (Aβ) protein plaques, which result from the sequential action of β-secretase and γ-secretase on amyloid precursor protein. Semagacestat is a small-molecule γ-secretase inhibitor that was developed as a potential treatment for Alzheimer’s disease.; Methods: We conducted a double-blind, placebo-controlled trial in which 1537 patients […]