A5012834716- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Neurological Disease Mechanisms and Treatments
- Inflammation biomarkers and pathways
- Tryptophan and brain disorders
- Immune cells in cancer
- Sleep and Wakefulness Research
- Cholesterol and Lipid Metabolism
- Neurogenesis and neuroplasticity mechanisms
- Medicinal Plants and Neuroprotection
- Adenosine and Purinergic Signaling
- Sleep and related disorders
- Hearing Loss and Rehabilitation
- Mitochondrial Function and Pathology
- Hormonal Regulation and Hypertension
- Hearing, Cochlea, Tinnitus, Genetics
- Liver Disease Diagnosis and Treatment
- Immune Response and Inflammation
- Nuclear Receptors and Signaling
- Ear Surgery and Otitis Media
- Endoplasmic Reticulum Stress and Disease
- Peroxisome Proliferator-Activated Receptors
- Neuroscience and Neuropharmacology Research
- Cerebrospinal fluid and hydrocephalus
Washington University in St. Louis
2019-2024
Hope Center for Neurological Disorders
2019-2024
University of Missouri–St. Louis
2023
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
Chronic activation of brain innate immunity is a prominent feature Alzheimer's disease (AD) and primary tauopathies. However, to what degree contributes neurodegeneration as compared with pathological protein-induced neurotoxicity, the requirement particular glial cell type in neurodegeneration, are still unclear. Here we demonstrate that microglia-mediated damage, rather than tau-induced direct leading force driving tauopathy mouse model. Importantly, progression ptau pathology also driven...
Abstract Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are critical for clearance myelin debris in areas demyelination, a key step to allow remyelination. TREM2 expressed microglia promotes microglial survival, proliferation, phagocytic activity. Herein we demonstrate that was highly on myelin-laden phagocytes active demyelinating lesions CNS subjects with MS. In gene...
The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer disease (AD). ApoE produced by both astrocytes and microglia in brain, whereas hepatocytes produce majority of apoE found periphery. Studies using APOE knock-in transgenic mice have demonstrated a strong isoform-dependent effect on accumulation amyloid-β (Aβ) deposition brain form Aβ-containing amyloid plaques cerebral angiopathy. However, specific contributions different pools to AD pathogenesis...
Apolipoprotein E (ApoE) genotype is the strongest genetic risk factor for late-onset Alzheimer's disease, with ε4 allele increasing in a dose-dependent fashion. In addition to ApoE4 playing crucial role amyloid-β deposition, recent evidence suggests that it also plays an important tau pathology and tau-mediated neurodegeneration. It not known, however, whether therapeutic reduction of would exert protective effects on neurodegeneration.Herein, we used antisense oligonucleotides (ASOs)...
Parenchymal border macrophages (PBMs) reside close to the central nervous system parenchyma and regulate CSF flow dynamics. We recently demonstrated that PBMs provide a clearance pathway for amyloid-β peptide, which accumulates in brain Alzheimer’s disease (AD). Given emerging role AD, we explored how tau pathology affects PBM populations PS19 mouse model of pathology. reduction flow, an increase MHCII + subpopulation mice compared with WT littermates. Consequently, asked whether dysfunction...
Abstract Background Extracellular amyloid‐β (Aβ) deposition as neuritic plaques and intracellular accumulation of hyperphosphorylated, aggregated tau neurofibrillary tangles (NFT) are two the characteristic hallmarks in Alzheimer’s disease (AD). The regional progression brain atrophy AD highly correlates with but not amyloid mechanisms tau‐mediated neurodegeneration clear. Innate immune responses represent a common pathway for initiation some neurodegenerative diseases. To date, little is...
Abstract Objective To describe the collection methods for perilymph fluid biopsy during cochlear implantation, detect levels of amyloid β 42 and 40 (Aβ Aβ ), total tau (tTau) analytes with a high‐precision assay, to compare these patient age Montreal Cognitive Assessment (MoCA) scores, explore potential mechanisms relationships otic pathology. Study Design Prospective study. Setting Tertiary referral center. Methods Perilymph was collected from 25 patients using polyimide tubing avoid...
Abstract Background Sleep disturbances are associated with the pathogenesis of neurodegenerative diseases including Alzheimer’s disease (AD) and primary tauopathies. We have previously shown that APOE4, strongest genetic risk factor for AD, directly influences severity key pathological hallmarks neurodegeneration tau deposition, microglial reactivity brain atrophy. loss accumulation in both mice humans, suggesting sleep may contribute to not only by influencing protein aggregation, but also...
APOE is the strongest genetic risk factor for late-onset Alzheimer’s disease. ApoE exacerbates tau-associated neurodegeneration by driving microglial activation. However, how apoE regulates activation and whether targeting therapeutically beneficial in tauopathy unclear. Here we show that overexpressing a low-density lipoprotein receptor (LDLR) transgene P301S tau transgenic mice markedly reduces brain ameliorates pathology neurodegeneration. specifically interacts with high-molecular-weight...
Abstract ApoE4 is the strongest genetic risk factor for late-onset Alzheimer Disease. It has been reported that apoE isoforms directly affect tauopathy and tau-mediated neurodegeneration in P301S tau transgenic mice expressing different human isoforms, with apoE4 resulting markedly increased absence of being marked protective against neurodegeneration. In brain, low-density lipoprotein receptor (LDLR) one main receptors regulates levels, but LDLR very few identified ligands compared to other...