000008314 001__ 8314
000008314 005__ 20240410114526.0
000008314 0247_ $$2DOI$$a10.6083/jd472x052
000008314 037__ $$aIR
000008314 245__ $$aInvestigating mechanisms that connect Alzheimer's disease with circadian disruptions
000008314 260__ $$bOregon Health and Science University
000008314 269__ $$a2020
000008314 336__ $$aAbstract
000008314 520__ $$aRecent research suggests that disruptions in circadian rhythms, including sleep-wake cycles, are early signs of Alzheimer's disease (AD) and may contribute to the pathological processes. The Amyloid Precursor Protein (APP) plays a key role in AD because when cleaved by β- and γ-secretase, it generates the toxic β-amyloid fragments. However, when α-secretase activity is followed by γ-secretase cleavage of APP, no β-amyloid is produced. Interestingly both APP processing pathways produce the same C-terminal APP intracellular domain (AICD), which has been linked to transcription regulation. Previous studies in Drosophila have shown that overexpression of α-secretase, β-secretase, or AICD in circadian pacemaker neurons disrupted locomotor activity rhythms. These studies suggest that the misregulation of APP processing and the consequent changes in AICD localization may contribute to the pathological processes in AD. To investigate how changes in the AICD function may contribute to AD, we used transgenic flies with induced AICD expression in circadian pacemaker neurons or mushroom body neurons.
000008314 540__ $$fCC BY
000008314 542__ $$fIn copyright - joint owners
000008314 650__ $$aCircadian Rhythm$$016745
000008314 650__ $$aAlzheimer Disease$$014513
000008314 650__ $$aDementia$$017461
000008314 650__ $$aNeurodegenerative Diseases$$031750
000008314 650__ $$aNeurocognitive Disorders$$032028
000008314 650__ $$aTauopathies$$033147
000008314 650__ $$acircadian pacemaker neurons
000008314 6531_ $$asleep-wake cycles
000008314 6531_ $$aamyloid precursor protein
000008314 6531_ $$aapp intracellular domain
000008314 692__ $$aOregon Institute of Occupational Health Sciences$$041496
000008314 7001_ $$aLong, Dani$$uOregon Health and Science University$$041354
000008314 7001_ $$aKretzschmar, Doris$$uOregon Health and Science University$$041354
000008314 711__ $$aResearch Week$$uOregon Health and Science University$$d2020
000008314 8564_ $$9dceec5c1-2790-4bff-90b6-eab8affb27d3$$s44434$$uhttps://digitalcollections.ohsu.edu/record/8314/files/ResearchWeek.2020.Long.Dani.pdf
000008314 905__ $$a/rest/prod/jd/47/2x/05/jd472x052
000008314 980__ $$aResearch Week