A5063316020- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Inflammation biomarkers and pathways
- Medicinal Plants and Neuroprotection
- MicroRNA in disease regulation
- Neurological Disease Mechanisms and Treatments
- Parkinson's Disease Mechanisms and Treatments
- Nuclear Receptors and Signaling
- Immune Response and Inflammation
- Chemokine receptors and signaling
- GDF15 and Related Biomarkers
- 14-3-3 protein interactions
- RNA Research and Splicing
- Bioinformatics and Genomic Networks
- Health, Environment, Cognitive Aging
- Neurological disorders and treatments
Cleveland Clinic
2016-2024
Cleveland Clinic Lerner College of Medicine
2017
Genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) confer increased risk developing late-onset Alzheimer's Disease (LOAD) and other neurodegenerative disorders. Recent studies provided insight into multifaceted roles TREM2 in regulating extracellular β-amyloid (Aβ) pathology, myeloid cell accumulation, inflammation observed AD, yet little is known regarding role intracellular microtubule associated protein tau (MAPT; tau) pathology diseases particular. Here we...
Background: Clinical trials of anti-Aβ monoclonal antibodies in Alzheimer disease (AD) infer target engagement from Aβ positron emission tomography (PET) and/or fluid biomarkers such as cerebrospinal (CSF) Aβ42/40.However, these measure deposits indirectly incompletely.In contrast, postmortem neuropathologic assessments allow direct investigation treatment effects on brain and many other pathologic features.Methods: From a clinical trial dominantly inherited AD, we measured...
Abstract INTRODUCTION The National Institute on Aging – Alzheimer's Association (NIA‐AA) ATN research framework proposes to use biomarkers for amyloid (A), tau (T), and neurodegeneration (N) stage individuals with AD pathological features track changes longitudinally. overall aim was utilize this characterize pre‐mortem status longitudinally in a clinically diagnosed cohort of dementia Lewy bodies (DLB) correlate it the post mortem diagnosis. METHODS subtyped by cerebrospinal fluid (CSF)...
Fractalkine (CX3CL1) and its receptor (CX3CR1) play an important role in regulating microglial function. We have previously shown that Cx3cr1 deficiency exacerbated tau pathology led to cognitive impairment. However, it is still unclear if the chemokine domain of ligand CX3CL1 essential neuronal pathology. used transgenic mice lacking endogenous Cx3cl1 (Cx3cl1−/−) expressing only obligatory soluble form (with domain) mucin stalk (referred as Cx3cl1105Δ mice) assess behavioral function both...
Alzheimer’s disease is the most common form of dementia, characterized by pathological accumulation amyloid-beta (Aβ) plaques and tau neurofibrillary tangles. Triggering receptor expressed on myeloid cells 2 (TREM2) increasingly recognized as playing a central role in Aβ clearance microglia activation AD. The TREM2 gene transcriptional product alternatively spliced to produce three different protein isoforms. canonical isoform binds DAP12 activate downstream pathways. However, little known...
Abstract Background Synuclein Aggregate Assays (SAA) in cerebrospinal fluid (CSF) and skin biopsy have been shown to successfully identify underlying synuclein (Lewy body) pathology patients with Parkinson's disease. Data Lewy Body Dementia (LBD) is limited, particularly pathologic confirmation staging of body pathology, other co‐pathologies. Method Utilizing data biofluids from participants the U.S. based Bodies Consortium (DLBC) who donated CSF study come autopsy, we examined performance...
Abstract Background Neuropathological hallmarks of AD, amyloid plaques and neurofibrillary tangles, have been described in dementia with Lewy bodies (DLB). Less is known about changes pre‐mortem cerebrospinal fluid (CSF) tau biomarker status DLB. CSF biomarkers for (A), (T), neurodegeneration (N) can be utilized to define pathological status. The overall aim this investigation was utilize the ATN research framework characterize AD‐related pathology longitudinally a rigorously characterized...
Abstract Background Cerebrospinal fluid (CSF) biomarkers for amyloid (A), tau (T), and neurodegeneration (N) can be utilized to define pre‐mortem pathological status (ATN research framework). However, potential differences across methods present challenges when comparing studies. Our objective was determine the ATN in an AD/ADRD cohort using two different measuring CSF AD‐related biomarkers; Fujirebio Lumipulse G1200 Luminex 200. The hypothesis that proportion of individuals a given category...
Recent reports in Alzheimer's Disease (AD) research suggests that alterations microRNA (miRNA) expression is associated with disease pathology. Our previous studies show genetic variation ADAM10 (A Disintegrin and Metalloproteinase 10) domain which encodes the major α-secretase responsible for cleaving Amyloid Precursor Protein (APP) with: higher CSF sAPP α levels cognitively normal controls compared AD patients along protein subjects low plaque scores those high scores, promoter activity...
Abstract Alzheimer’s disease (AD) is characterized by the accumulation in brain of extracellular amyloid β (Aβ) plaques as well intraneuronal inclusions (neurofibrillary tangles) consisting total tau and phosphorylated tau. Also present are dystrophic neurites, loss synapses, neuronal death, gliosis. AD genetic studies have highlighted importance inflammation this identifying several risk associated immune response genes, including TREM2. TREM2 has been strongly implicated basic microglia...