PMC:6582309 / 50461-51784
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6582309","sourcedb":"PMC","sourceid":"6582309","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6582309","text":"To date, most of the drugs in development for AD treatment have been directed toward the removal of amyloid plaques or NFTs, not taking into the account the multifactorial causation of the disease. Several experimental drugs that have successfully removed plaques from mouse brains have not lessened the symptoms of AD in people. For instance, drugs acting as BACE1 (beta-site amyloid precursor protein cleaving enzyme-1) inhibitors had failed in Phase II/III clinical trials (Hawkes, 2017; Dobrowolska Zakaria and Vassar, 2018; Egan et al., 2018). A BACE1 inhibitor verubecestat successfully blocked the accumulation of amyloid protein in mice (Villarreal et al., 2017), rats and monkeys (Kennedy et al., 2016), but did not reduce cognitive or functional decline in patients with mild to moderate AD (Egan et al., 2018). Although decrease in Aβ biomarkers in CSF and brain has been noticed after treatment with BACE1 inhibitors, the failure to prevent cognitive decline might have been due to irreversible neurotoxic accumulation of Aβ that occurred prior to the start of the treatment. For this reason, focus is on the development of therapies that commence at presymptomatic stage (preclinical stage and the stage of mild cognitive impairment) although for this, development of novel, useful biomarkers, is also crucial.","tracks":[{"project":"2_test","denotations":[{"id":"31249505-28202490-38601735","span":{"begin":485,"end":489},"obj":"28202490"},{"id":"31249505-30322841-38601736","span":{"begin":523,"end":527},"obj":"30322841"},{"id":"31249505-29719179-38601737","span":{"begin":542,"end":546},"obj":"29719179"},{"id":"31249505-28800329-38601738","span":{"begin":665,"end":669},"obj":"28800329"},{"id":"31249505-27807285-38601739","span":{"begin":706,"end":710},"obj":"27807285"},{"id":"31249505-29719179-38601740","span":{"begin":815,"end":819},"obj":"29719179"}],"attributes":[{"subj":"31249505-28202490-38601735","pred":"source","obj":"2_test"},{"subj":"31249505-30322841-38601736","pred":"source","obj":"2_test"},{"subj":"31249505-29719179-38601737","pred":"source","obj":"2_test"},{"subj":"31249505-28800329-38601738","pred":"source","obj":"2_test"},{"subj":"31249505-27807285-38601739","pred":"source","obj":"2_test"},{"subj":"31249505-29719179-38601740","pred":"source","obj":"2_test"}]},{"project":"0_colil","denotations":[{"id":"31249505-28202490-737160","span":{"begin":485,"end":489},"obj":"28202490"},{"id":"31249505-30322841-737161","span":{"begin":523,"end":527},"obj":"30322841"},{"id":"31249505-29719179-737162","span":{"begin":542,"end":546},"obj":"29719179"},{"id":"31249505-28800329-737163","span":{"begin":665,"end":669},"obj":"28800329"},{"id":"31249505-27807285-737164","span":{"begin":706,"end":710},"obj":"27807285"},{"id":"31249505-29719179-737165","span":{"begin":815,"end":819},"obj":"29719179"}],"attributes":[{"subj":"31249505-28202490-737160","pred":"source","obj":"0_colil"},{"subj":"31249505-30322841-737161","pred":"source","obj":"0_colil"},{"subj":"31249505-29719179-737162","pred":"source","obj":"0_colil"},{"subj":"31249505-28800329-737163","pred":"source","obj":"0_colil"},{"subj":"31249505-27807285-737164","pred":"source","obj":"0_colil"},{"subj":"31249505-29719179-737165","pred":"source","obj":"0_colil"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#96ec93","default":true},{"id":"0_colil","color":"#ec93b0"}]}]}}