TY  - GEN
N2  - Recent 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.
DO  - 10.6083/jd472x052
DO  - DOI
AB  - Recent 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.
AD  - Oregon Health and Science University
AD  - Oregon Health and Science University
T1  - Investigating mechanisms that connect Alzheimer's disease with circadian disruptions
DA  - 2020
AU  - Long, Dani
AU  - Kretzschmar, Doris
L1  - https://digitalcollections.ohsu.edu/record/8314/files/ResearchWeek.2020.Long.Dani.pdf
PB  - Oregon Health and Science University
PY  - 2020
ID  - 8314
L4  - https://digitalcollections.ohsu.edu/record/8314/files/ResearchWeek.2020.Long.Dani.pdf
KW  - Circadian Rhythm
KW  - Alzheimer Disease
KW  - Dementia
KW  - Neurodegenerative Diseases
KW  - Neurocognitive Disorders
KW  - Tauopathies
KW  - circadian pacemaker neurons
KW  - sleep-wake cycles
KW  - amyloid precursor protein
KW  - app intracellular domain
TI  - Investigating mechanisms that connect Alzheimer's disease with circadian disruptions
Y1  - 2020
L2  - https://digitalcollections.ohsu.edu/record/8314/files/ResearchWeek.2020.Long.Dani.pdf
LK  - https://digitalcollections.ohsu.edu/record/8314/files/ResearchWeek.2020.Long.Dani.pdf
UR  - https://digitalcollections.ohsu.edu/record/8314/files/ResearchWeek.2020.Long.Dani.pdf
ER  -