A5068679708- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Dementia and Cognitive Impairment Research
- Inflammation biomarkers and pathways
- Neurological Disease Mechanisms and Treatments
- Parkinson's Disease Mechanisms and Treatments
- MicroRNA in disease regulation
- Bioinformatics and Genomic Networks
- Tryptophan and brain disorders
- Nuclear Receptors and Signaling
- Advanced Neuroimaging Techniques and Applications
- Functional Brain Connectivity Studies
- Computational Drug Discovery Methods
- Genetic Associations and Epidemiology
- Amyotrophic Lateral Sclerosis Research
- Health, Environment, Cognitive Aging
- Neurological diseases and metabolism
- Diabetes and associated disorders
- Folate and B Vitamins Research
- S100 Proteins and Annexins
- 14-3-3 protein interactions
- Cholinesterase and Neurodegenerative Diseases
- Intracerebral and Subarachnoid Hemorrhage Research
- GDF15 and Related Biomarkers
- Amyloidosis: Diagnosis, Treatment, Outcomes
Cleveland Clinic
2016-2025
Cleveland Clinic Lerner College of Medicine
2015-2024
University of Pennsylvania
2007-2024
Thomas Jefferson University
2024
University of Miami
2024
University of California, San Diego
2024
Western University
2024
Western University of Health Sciences
2024
Children's Hospital of Western Ontario
2024
Australian National University
2024
Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer’s disease (AD) and other neurodegenerative diseases. However, the cell types mechanisms underlying TREM2’s involvement neurodegeneration remain to be established. Here, we report that TREM2 is up-regulated surrounding amyloid deposits AD mouse models human tissue. was detected CD45hiLy6C+ cells, but not P2RY12+ parenchymal microglia. In mice deficient TREM2, macrophages are virtually...
PAR promotes α-synuclein toxicity How pathologic (α-syn) leads to neurodegeneration in Parkinson's disease (PD) remains poorly understood. Kam et al. studied the α-syn preformed fibril (α-syn PFF) model of sporadic PD (see Perspective by Brundin and Wyse). They found that α-syn–activated poly(adenosine 5′-diphosphate–ribose) (PAR) polymerase–1 (PARP-1) inhibition PARP or knockout PARP-1 protected mice from pathology. The generation PFF–induced activation converted PFF a strain was 25-fold...
<h3>Background</h3> Mutation in the progranulin gene (<i>GRN</i>) can cause frontotemporal dementia (FTD). However, it is unclear whether some rare FTD-related<i>GRN</i>variants are pathogenic and neurodegenerative disorders other than FTD also be caused by<i>GRN</i>mutations. <h3>Objectives</h3> To delineate range of clinical presentations associated with<i>GRN</i>mutations to define candidacy rare<i>GRN</i>variants. <h3>Design</h3> Case-control study. <h3>Setting</h3> Clinical...
Background Brain-derived neurotrophic factor (BDNF) is an activity-dependent secreted protein that critical to organization of neuronal networks and synaptic plasticity, especially in the hippocampus. We tested hypothesis reduced CSF BDNF associated with age-related cognitive decline. Methodology/Principal Findings, Conclusions/Significance concentration BDNF, Aβ42 total tau were measured 128 cognitively normal adults (Normals), 21 patients Alzheimer's disease (AD), nine Mild Cognitive...
MicroRNA (miRNA) may be potential biomarkers of Alzheimer's disease (AD). The objective this investigation was to demonstrate that miRNAs in human brain or biofluids are differentially expressed according status, tissue type, neuritic plaque score Braak stage. Post-mortem (PMB) miRNA were profiled using arrays and validated quantitative RT-PCR (qRT-PCR). Five qRT-PCR-validated measured an independent sample PMB, cerebrospinal fluid plasma from the same subjects. Plasma miR-15a found...
Abstract Background Recent DNA/RNA sequencing and other multi-omics technologies have advanced the understanding of biology pathophysiology AD, yet there is still a lack disease-modifying treatments for AD. A new approach to integration genome, transcriptome, proteome, human interactome in drug discovery development process essential this endeavor. Methods In study, we developed AlzGPS ( G enome-wide P ositioning S ystems platform Alz heimer’s Drug Discovery, https://alzgps.lerner.ccf.org ),...
Because disease-associated microglia (DAM) and astrocytes (DAA) are involved in the pathophysiology of Alzheimer's disease (AD), we systematically identified molecular networks between DAM DAA to uncover novel therapeutic targets for AD. Specifically, develop a network-based methodology that leverages single-cell/nucleus RNA sequencing data from both transgenic mouse models AD patient brains, as well drug-target network, metabolite-enzyme associations, human protein-protein interactome,...
Abstract Background The relationship between biomarkers of metabolic syndrome and insulin resistance, plasma triglyceride/HDL cholesterol (TG/HDL-C) ratio, on the rate cognitive decline in mild impairment (MCI) dementia stages Alzheimer’s disease (AD) is unknown. role peripheral cerebrospinal fluid (CSF) levels Apolipoprotein A1 (ApoA1), a key functional component HDL, also remains unclear among them. Here we evaluate baseline TG/HDL-C ratio CSF ApoA1 their relation with MCI Dementia AD....
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...
The gene GAD2 encoding the glutamic acid decarboxylase enzyme (GAD65) is a positional candidate for obesity on Chromosome 10p11–12, susceptibility locus morbid in four independent ethnic populations. GAD65 catalyzes formation of γ-aminobutyric (GABA), which interacts with neuropeptide Y paraventricular nucleus to contribute stimulate food intake. A case-control study (575 morbidly obese and 646 control subjects) analyzing variants identified both protective haplotype, including most frequent...
Mutations in the progranulin (GRN) gene have recently been reported as a cause of frontotemporal dementia (FTD) syndrome. We performed clinical, neuropathological and molecular genetic study two families with FTD same novel mutation GRN. Age onset ranged from 35 to 75 years all individuals progressed severe syndrome mean disease duration ∼6–10 years. Variable clinical presentations included language impairment, behaviour change or parkinsonism. Seven total autopsies (five Family 1, 2) showed...
The clinical diagnosis of dementia with Lewy bodies (DLB) depends on identifying significant cognitive decline accompanied by core features parkinsonism, visual hallucinations, fluctuations, and REM sleep behavior disorder (RBD). Hyposmia is one the several supportive features. α-Synuclein seeding amplification assays (αSyn-SAAs) may enhance diagnostic accuracy detecting pathologic αSyn seeds in CSF. In this study, we examine how different associate CSF αSyn-SAA positivity a large group...
This study tests the hypothesis that certain MRI-based regional brain volumes will show reductions over time in a cohort exposed to repetitive head impacts (RHI).Participants were drawn from Professional Fighters Brain Health Study, longitudinal observational of professional fighters and controls. Participants underwent annual 3T MRI, computerized cognitive testing, blood sampling for determination neurofilament light (NfL) tau levels. Yearly change volume was calculated several...
Abstract Introduction Recent advances in generating massive single‐cell/nucleus transcriptomic data have shown great potential for facilitating the identification of cell type–specific Alzheimer's disease (AD) pathobiology and drug‐target discovery therapeutic development. Methods We developed The Cell Atlas (TACA) by compiling an AD brain atlas consisting over 1.1 million cells/nuclei across 26 sets, covering major regions (hippocampus, cerebellum, prefrontal cortex, so on) types...