A5066821454- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Lysosomal Storage Disorders Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Cellular transport and secretion
- Sleep and Wakefulness Research
- Mitochondrial Function and Pathology
- Microtubule and mitosis dynamics
- RNA regulation and disease
- Diet and metabolism studies
- Dementia and Cognitive Impairment Research
- Neurotransmitter Receptor Influence on Behavior
- Adipose Tissue and Metabolism
- Functional Brain Connectivity Studies
- Neurogenesis and neuroplasticity mechanisms
- Virus-based gene therapy research
- Neurological Disease Mechanisms and Treatments
- Sleep and related disorders
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Extracellular vesicles in disease
- Trypanosoma species research and implications
- Immune cells in cancer
- Ion channel regulation and function
- Regulation of Appetite and Obesity
- Tryptophan and brain disorders
University of Kentucky
2023-2025
Wake Forest University
2019-2024
Winston-Salem/Forsyth County Schools
2023
Diabetes Australia
2023
Alzheimer’s Disease Neuroimaging Initiative
2023
Columbia University Irving Medical Center
2021
Hope Center for Neurological Disorders
2015-2018
Washington University in St. Louis
2005-2017
University of Washington
2015
See Mander et al. (doi:10.1093/awx174) for a scientific commentary on this article. Sleep deprivation increases amyloid-β, suggesting that chronically disrupted sleep may promote amyloid plaques and other downstream Alzheimer's disease pathologies including tauopathy or inflammation. To date, studies have not examined which aspect of modulates amyloid-β biomarkers. Seventeen healthy adults (age 35–65 years) without disorders underwent 5–14 days actigraphy, followed by slow wave activity...
Epidemiological studies show that patients with type 2 diabetes (T2DM) and individuals a diabetes-independent elevation in blood glucose have an increased risk for developing dementia, specifically dementia due to Alzheimer's disease (AD). These observations suggest abnormal metabolism likely plays role some aspects of AD pathogenesis, leading us investigate the link between aberrant metabolism, T2DM, murine models. Here, we combined two techniques – clamps vivo microdialysis as means...
Aerobic glycolysis and lactate production in the brain plays a key role memory, yet of this metabolism cognitive decline associated with Alzheimer's disease (AD) remains poorly understood. Here we examined relationship between cerebral levels memory performance an APP/PS1 mouse model AD, which progressively accumulates amyloid-β. In vivo 1 H-magnetic resonance spectroscopy revealed age-dependent within frontal cortex control mice, whereas remained unaltered mice from 3 to 12 months age....
Abstract Brain‐derived extracellular vesicles (EVs) play an active role in Alzheimer's disease (AD), relaying important physiological information about their host tissues. The internal cargo of EVs is protected from degradation, making attractive AD biomarkers. However, it unclear how circulating relate to isolated disease‐vulnerable brain regions. We developed a novel method for collecting the hippocampal interstitial fluid (ISF) live mice. (EV ISF ) were via ultracentrifugation and...
Mutations in the CLN2 gene, which encodes a lysosomal serine protease, tripeptidyl-peptidase I (TPP I), result an autosomal recessive neurodegenerative disease of children, classical late-infantile neuronal ceroid lipofuscinosis (cLINCL). cLINCL is inevitably fatal, and there currently exists no cure or effective treatment. In this report, we provide characterization first CLN2-targeted mouse model for cLINCL. mice were fertile apparently healthy at birth despite absence detectable TPP...
Infantile neuronal ceroid lipofuscinosis (INCL) is an inherited neurodegenerative disorder affecting the CNS during infancy. INCL caused by mutations in CLN1 gene that lead to a deficiency lysosomal hydrolase, palmitoyl protein thioesterase 1 (PPT1). A murine model of INCL, PPT1-deficient ( PPT1 −/− ) mouse, accurate phenocopy human disease. The first pathological change observed brain regional areas glial fibrillary acidic (GFAP) upregulation, which predicts future neurodegeneration. We...
Neuronal ceroid lipofuscinoses (NCLs; Batten disease) are collectively the most frequent autosomal-recessive neurodegenerative disease of childhood, but underlying cellular and molecular mechanisms remain unclear.Several lines evidence have highlighted important role that non-somatic compartments neurons (axons synapses) play in instigation progression NCL pathogenesis.Here, we report a progressive breakdown axons synapses brains two different mouse models NCL: Ppt1 2/2 model infantile Cln6...
Hyperinsulinemia is a risk factor for late-onset Alzheimer9s disease (AD). <i>In vitro</i> experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but <i>in vivo</i> are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving <i>APP<sub>swe</sub></i>/<i>PS1<sub>dE9</sub></i> transgenic mice. Both postprandial...
Infantile neuronal ceroid lipofuscinosis (INCL) is a neurodegenerative disorder caused by mutations in the gene encoding lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). The earliest clinical sign INCL blindness, followed seizures, cognitive deficits, and early death. Little known about progression of visual deficits INCL. Here we characterize progressive retinal dysfunction examine efficacy AAV2-mediated ocular therapy murine model Significant decreases both mixed rod/cone pure...
Niemann-Pick A disease (NPA) is a fatal lysosomal storage disorder caused by deficiency in acid sphingomyelinase (ASM) activity. The lack of functional ASM results cellular accumulation sphingomyelin and cholesterol within distended lysosomes throughout the brain. In this study, we investigated potential AAV-mediated expression to correct brain pathology an knockout (ASMKO) mouse model NPA. An AAV serotype 2 vector encoding human (AAV2-hASM) was injected directly into adult ASMKO hippocampus...
Globoid-cell leukodystrophy (GLD) is an inherited demyelinating disease caused by the deficiency of lysosomal enzyme galactosylceramidase (GALC). A previous study in murine model GLD (twitcher) demonstrated a dramatic synergy between CNS-directed adeno-associated virus 2/5 (AAV2/5) gene therapy and myeloreductive bone marrow transplantation (BMT). However, mechanism which these two disparate therapeutic approaches synergize not clear. In addition, efficacy may have been limited since was...
Infantile neuronal ceroid lipofuscinosis (INCL) is an inherited childhood neurodegenerative disorder caused by the loss of palmitoyl protein thioesterase-1 (PPT1) activity. Affected children suffer from blindness, epilepsy, motor dysfunction, cognitive decline, and premature death. The Ppt1(-/-) mouse shares histological clinical features INCL. Previous single-therapy approaches using small molecule drugs, gene therapy, or stem cells resulted in partial correction, with minimal improvements...
Infantile neuronal ceroid lipofuscinosis (INCL) is an inherited neurodegenerative lysosomal storage disease (LSD) caused by a deficiency in palmitoyl protein thioesterase-1 (PPT1). Studies Ppt1(-/-) mice demonstrate that glial activation central to the pathogenesis of INCL. Astrocyte precedes loss, while cytokine upregulation associated with microglial reactivity occurs before and concurrent neurodegeneration. Therefore, we hypothesized cascades neuroinflammation are important therapeutic...
Epidemiological studies identified alcohol use disorder (AUD) as a risk factor for Alzheimer's disease (AD), yet there is conflicting evidence on how promotes AD pathology. In this study, 10-week moderate two-bottle choice drinking paradigm was used to identify chronic ethanol exposure alters amyloid-β (Aβ)-related pathology, metabolism, and behavior. Ethanol-exposed APPswe/PSEN1dE9 (APP/PS1) mice showed increased brain atrophy an number of amyloid plaques. Further analysis revealed that led...
Elevated blood glucose levels, or hyperglycemia, can increase brain excitability and amyloid-β (Aβ) release, offering a mechanistic link between type 2 diabetes Alzheimer's disease (AD). Since the cellular mechanisms governing this relationship are poorly understood, we explored whether ATP-sensitive potassium (KATP) channels, which couple changes in energy availability with excitability, play role AD pathogenesis. First, demonstrate that KATP channel subunits Kir6.2/KCNJ11 SUR1/ABCC8 were...
Niemann-Pick disease is caused by a genetic deficiency in acid sphingomyelinase (ASM) leading to the intracellular accumulation of sphingomyelin and cholesterol lysosomes. In present study, we evaluated effects direct intracerebral transplantation neural progenitor cells (NPCs) on brain storage pathology ASM knock-out (ASMKO) mouse model Type A disease. NPCs derived from adult were genetically modified express human (hASM) transplanted into multiple regions ASMKO brain. Transplanted...
Globoid-cell leukodystrophy (GLD) is a rapidly progressing inherited neurodegenerative disorder caused by deficiency in galactosylceramidase activity. Previous studies the murine model of GLD (Twitcher mouse) have shown that both bone marrow transplantation (BMT) and central nervous system (CNS)-directed gene therapy can be moderately effective at ameliorating certain aspects GLD. As BMT CNS-directed target fundamentally different tissues, we tested hypothesis combining these disparate...