A5065578455- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Sleep and Wakefulness Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Diet and metabolism studies
- Mitochondrial Function and Pathology
- Functional Brain Connectivity Studies
- Trypanosoma species research and implications
- Retinal Development and Disorders
- Epilepsy research and treatment
- Genetics, Aging, and Longevity in Model Organisms
- Neurological disorders and treatments
- Genetic Neurodegenerative Diseases
- Neurobiology and Insect Physiology Research
- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Peroxisome Proliferator-Activated Receptors
- Genetics and Neurodevelopmental Disorders
- Sleep and related disorders
- Adipose Tissue and Metabolism
Washington University in St. Louis
2021
Hope Center for Neurological Disorders
2014-2019
Baylor College of Medicine
2012-2018
NeuroDevelopment Center
2013
Sleep may protect the brain from AD Two main proteins accumulate in Alzheimer's disease (AD), β-amyloid (Aβ) and tau. Aβ appears to instigate AD, but tau drive damage cognitive decline. deprivation is known increase acutely chronically. Now, Holth et al. show that chronic sleep strongly increases over hours also drives pathology spreading brains of mice humans (see Perspective by Noble Spires-Jones). Thus, have a direct protective effect on key protein pathology. Science , this issue p. 880 ; see 813
Tau is primarily a cytoplasmic protein that stabilizes microtubules. However, it also found in the extracellular space of brain at appreciable concentrations. Although its presence there may be relevant to intercellular spread tau pathology, cellular mechanisms regulating release into are not well understood. To test this context neuronal networks vivo, we used vivo microdialysis. Increasing activity rapidly increased steady-state levels vivo. Importantly, presynaptic glutamate sufficient...
Neuronal network hyperexcitability underlies the pathogenesis of seizures and is a component some degenerative neurological disorders such as Alzheimer's disease (AD). Recently, microtubule-binding protein tau has been implicated in regulation synchronization. Genetic removal Mapt , gene encoding tau, AD models overexpressing amyloid-β (Aβ) decreases normalizes excitation/inhibition imbalance. Whether this effect specific to Aβ mouse remains be determined. Here, we examined an excitability...
Sleep disorders are prevalent in Alzheimer's disease (AD) and a major cause of institutionalization. Like AD pathology, sleep abnormalities can appear years before cognitive decline may be predictive dementia. A bidirectional relationship between amyloid β (Aβ) has been well established with disturbed increased wakefulness leading to Aβ production decreased clearance; whereas deposition is associated disturbances. fluctuates the wake cycle higher during lower sleep. This fluctuation lost...
Sleep disturbances are prevalent in human tauopathies yet despite the importance of sleep, little is known about its relationship with tau pathology. Here, we investigate this interaction by analyzing sleep and pathology throughout tauopathy disease progression P301S transgenic mice.P301S wild-type mice were analyzed electroencephalography (EEG)/electromyography at 3, 6, 9, 11 months age for sleep/wake time, EEG power, homeostatic response. Cortical volume was also assessed anti-phospho-tau...
We report the identification and characterization of a previously unknown suppressor myopathy caused by expansion CUG repeats, mutation that triggers Myotonic Dystrophy Type 1 (DM1). screened collection genes encoding RNA–binding proteins as candidates to modify DM1 pathogenesis using well established Drosophila model disease. The screen revealed smaug powerful modulator CUG-induced toxicity. Increasing levels prevents muscle wasting restores function, while reducing its function exacerbates...
Vascular disease contributes to neurodegeneration, which is associated with decreased blood pressure in older humans. Plasmalogens, ether phospholipids produced by peroxisomes, are Alzheimer's disease, Parkinson's and other neurodegenerative disorders. However, the mechanistic links between phospholipids, pressure, neurodegeneration not fully understood. Here, we show that endothelium-derived affect behavior, mice. In young adult mice, inducible endothelial-specific disruption of PexRAP, a...
Deletion of Mapt, encoding the microtubule-binding protein Tau, prevents disease in multiple genetic models hyperexcitability. To investigate whether effect Tau depletion is generalizable across sodium channel gene-linked epilepsy, we examined Scn1b-/- mouse model Dravet syndrome, and Scn8aN1768D/+ Early Infantile Epileptic Encephalopathy. Both display severe seizures early mortality. We found no prolongation survival between Scn1b-/-,Mapt+/+ , Scn1b-/-,Mapt+/-, or Scn1b-/-,Mapt-/- mice...
For 25 years, Alzheimer's disease (AD) has been recognized as a clinical risk factor for late onset seizures. AD and epilepsy share similar atrophic metabolic changes in the human brain most familial gene mutations lead to epilepsy. In addition, multiple mouse models overexpressing Aß exhibit spontaneous seizures remodeled circuitry that seen Aggregation of microtubule binding protein tau is one hallmark AD. Deletion Tau suppresses normalizes synaptic imbalance an model, suggesting regulates...