A5072844770- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Endoplasmic Reticulum Stress and Disease
- RNA regulation and disease
- Amyotrophic Lateral Sclerosis Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenetic and Muscular Disorders Research
- Dementia and Cognitive Impairment Research
- Protein Structure and Dynamics
- Cellular transport and secretion
- Advanced Neuroimaging Techniques and Applications
- Cerebrovascular and genetic disorders
- Microbial metabolism and enzyme function
- Genomic variations and chromosomal abnormalities
- Cerebrovascular and Carotid Artery Diseases
- Genomics and Rare Diseases
- Galectins and Cancer Biology
- Salivary Gland Tumors Diagnosis and Treatment
- RNA Research and Splicing
- Sinusitis and nasal conditions
- interferon and immune responses
- Chromosomal and Genetic Variations
- Acute Ischemic Stroke Management
- Head and Neck Surgical Oncology
University of California, San Diego
2020-2024
Massachusetts General Hospital
2015-2021
Discovery Institute
2021
Sanford Burnham Prebys Medical Discovery Institute
2021
Harvard University
2015-2017
MaineGeneral Medical Center
2015-2017
Brigham and Women's Hospital
2012
To examine region- and substrate-specific autoradiographic in vitro binding patterns of positron emission tomography tracer [F-18]-AV-1451 (previously known as T807), tailored to allow vivo detection paired helical filament-tau-containing lesions, determine whether there is off-target other amyloid/non-amyloid proteins.We applied phosphor screen autoradiography, nuclear emulsion [H-3]-AV-1451 assays the study postmortem samples from patients with a definite pathological diagnosis Alzheimer...
Abstract Tau pathology is known to spread in a hierarchical pattern Alzheimer’s disease (AD) brain during progression, likely by trans-synaptic tau transfer between neurons. However, the species involved inter-neuron propagation remains unclear. To identify responsible for propagation, we examined uptake and properties of different derived from postmortem cortical extracts interstitial fluid tau-transgenic mice, as well human AD cortices. Here show that PBS-soluble phosphorylated...
Objective Recent studies have shown that positron emission tomography (PET) tracer AV-1451 exhibits high binding affinity for paired helical filament (PHF)-tau pathology in Alzheimer's brains. However, the ability of this ligand to bind tau lesions other tauopathies remains controversial. Our goal was examine correlation vivo and postmortem patterns three autopsy-confirmed non-Alzheimer tauopathy cases. Methods We quantified retention [F-18]-AV-1451 performed autoradiography, [H-3]-AV-1451...
Complement components and their receptors are found within around amyloid β (Aβ) cerebral plaques in Alzheimer's disease (AD). Microglia defend against pathogens through phagocytosis via complement component C3 and/or engagement of cleavage product iC3b with receptor type 3 (CR3, Mac-1). Here, we provide direct evidence that Mac-1 mediate, part, clearance fibrillar amyloid-β (fAβ) by murine microglia vitro vivo. took up not only synthetic fAβ(42) but also cores from patients AD, transporting...
Cerebral amyloid angiopathy is a common neuropathological finding in the ageing human brain, associated with cognitive impairment. Neuroimaging markers of severe cerebral are cortical microbleeds and microinfarcts. These parenchymal brain lesions considered key contributors to Therefore, they important targets for therapeutic strategies may serve as surrogate neuroimaging clinical trials. We aimed gain more insight into pathological basis magnetic resonance imaging-defined microinfarcts...
Cerebrospinal fluid (CSF) tau is an excellent surrogate marker for assessing neuropathological changes that occur in Alzheimer's disease (AD) patients. However, whether the elevated AD CSF just a of neurodegeneration or, fact, part process uncertain. Moreover, it unknown how relates to recently described soluble high-molecular-weight (HMW) species found postmortem brain and can be taken up by neurons seed aggregates.We have examined seeding uptake properties extracellular from various...
Triggers of innate immune signaling in the CNS patients with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD) remain elusive. We report presence cytoplasmic double-stranded RNA (cdsRNA), an established trigger immunity, ALS-FTD brains carrying
Abstract Aggregation of Aβ amyloid fibrils into plaques in the brain is a universal hallmark Alzheimer’s Disease (AD), but whether different individuals are equivalent unknown. One possibility that exhibit structures and may contribute differentially to disease, either within an individual or between individuals. However, occurrence distribution structural polymorphisms human poorly documented. Here we use X-ray microdiffraction histological sections tissue map abundance, orientation...
Neuropathological and genetic findings suggest that the presynaptic protein α-synuclein (aSyn) is involved in pathogenesis of synucleinopathy disorders, including Parkinson's disease (PD), dementia with Lewy bodies (DLB) multiple system atrophy. Evidence suggests self-assembly aSyn conformers bound to phospholipid membranes an aggregation-prone state plays a key role neurotoxicity. Accordingly, we hypothesized binding partners lipid-associated could inhibit formation toxic oligomers at...
SUMMARY Innate immune signaling activation and DNA damage are pathological hallmarks of aging that may herald multiple adult-onset neurodegenerative diseases. Here, we report both cell autonomous non-autonomous neuronal death triggered by the production cytoplasmic double-stranded RNA (cdsRNA) from a regulated, disarticulated transgene in setting type I interferon (IFN-I) signaling. CdsRNA is pathogen associated molecular pattern induces IFN-I many types. Transfection dsRNA mimetic into...
Abstract Background Facial baroparesis is a palsy of the seventh cranial nerve resulting from increased pressure compressing along its course through middle ear cavity. It rare condition, most commonly reported in barotraumatic environments, particular scuba diving and high-altitude air travel. We report here an unusual case highly frequent baroparesis, workup, successful treatment. Case presentation A 57-year-old Caucasian male commercial airline traveler presented with 4-year history...
To describe the neuropathologic and splicing changes in RNA binding protein (RBP) ELAVL3 amyotrophic lateral sclerosis (ALS) frontotemporal lobar degeneration (FTLD).
Oligomerization of the presynaptic protein aSyn is thought to play a key role in pathogenesis PD. exists number conformations, including membrane‐bound state likely involved regulating synaptic vesicle trafficking. interacts with anionic phospholipid vesicles by forming an amphipathic α‐helix various lengths. We hypothesize that disruption interactions between and membranes leads shift short‐helix, lipid‐bound form, which more susceptible toxic oligomers due exposure protein's central...
Tau pathology is known to spread in a hierarchical pattern the brains of patients with Alzheimer's disease (AD) during progression, likely via trans-synaptic tau transfer between neurons. Our previous findings suggest that rare species soluble phosphorylated high-molecular-weight (HMW) Tau, derived from transgenic mice and human AD brains, endogenous form involved propagation. In this study, we examined cerebrospinal fluid (CSF) control subjects, also postmortem ventricular CSF determine if...