Distinct forms of amyloid-β moderate sleep duration through NAD+-linked redox metabolism in Alzheimer's disease.
Yu, Y.; Fedele, G.; Celardo, I.; Zhou, L.; Tan, B.; Loh, S.; Martins, L. M.
Show abstract
Sleep disruptions precede a clinical diagnosis of Alzheimers disease (AD) by several years. However, how AD pathologies affect sleep remains unclear. Here, we integrate epidemiological data with insights from Drosophila models of AD to investigate how AD progression could be linked to sleep disruption. We found that individuals with a high risk of AD report a shorter sleep duration than do those with a clinical diagnosis of AD. We showed that the expression of different forms of amyloid-{beta} in flies can replicate these variations in sleep duration. Analysis of the metabolome and proteome of these flies revealed distinct changes in NAD+-linked redox metabolism and levels of hyperkinetic (Hk), a redox-sensing sleep homeostat. We showed that the genetic upregulation of Hk is neuroprotective and increased KCNAB2 expression in the brain decreases AD risk in humans. Overall, our data provides a new mechanism linking the disruption of NAD+-linked redox sensing and sleep disruption in AD.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Downregulation of Dickkopf-3, a Wnt antagonist elevated in Alzheimer's disease, restores synapse integrity and memory in a disease mouse model 95%
- Iron-sulfur cluster loss in mitochondrial CISD1 mediates PINK1 loss-of-function phenotypes 94%
- Unraveling the link between Neuropathy Target Esterase NTE/SWS, lysosomal storage diseases, inflammation, and abnormal fatty acid metabolism 93%
Similar papers in this journal
- ZCCHC17 modulates neuronal RNA splicing and supports cognitive resilience in Alzheimer's disease 94%
- Amelioration of symptomatic Alzheimer's Disease after selective impairment of p75NTR function in adult forebrainexcitatory neurons 94%
- Dietary Amino Acids Impact LRRK2-induced Neurodegeneration in Parkinson's Disease Models 93%
Similar papers in this journal
Similar papers in this journal
- Modelling human neuronal catecholaminergic pigmentation in rodents recapitulates age-related multisystem neurodegenerative deficits 94%
- Integrative analysis reveals a conserved role for the amyloid precursor protein in proteostasis during aging 94%
- Identification of Chlamydia pneumoniae and NLRP3 inflammasome activation in Alzheimer's disease retina 93%
Similar papers in this journal
- Tunable Tau Expression in C. elegans Neurons Reveals that Early-AD Tau Phosphorylation Selectively Impacts Behavior and Mitochondrial Quality Control 94%
- Interictal Spikes in Alzheimer's Disease: Preclinical Evidence for Dominance of the Dentate Gyrus and Cholinergic Control by Medial Septum 94%
- Immune receptor LAG3 regulates microglia function duringAlzheimer's disease 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.