Hamilton Oh
A5051420413- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Single-cell and spatial transcriptomics
- Health, Environment, Cognitive Aging
- Neurological Disease Mechanisms and Treatments
- Mitochondrial Function and Pathology
- Genetics, Aging, and Longevity in Model Organisms
- Advanced Proteomics Techniques and Applications
- Immune cells in cancer
- Dementia and Cognitive Impairment Research
- Inflammation biomarkers and pathways
- Bioinformatics and Genomic Networks
- Nutritional Studies and Diet
- Spaceflight effects on biology
- Neuroethics, Human Enhancement, Biomedical Innovations
- Parkinson's Disease Mechanisms and Treatments
- Nutrition and Health in Aging
- Genetic Neurodegenerative Diseases
- Olfactory and Sensory Function Studies
- Neuroscience and Neuropharmacology Research
- Adipose Tissue and Metabolism
- Zebrafish Biomedical Research Applications
- Physical Activity and Health
- Diet and metabolism studies
- Metabolomics and Mass Spectrometry Studies
Stanford University
2020-2025
Neurosciences Institute
2021-2025
UCLA Health
2018
Abstract Animal studies show aging varies between individuals as well organs within an individual 1–4 , but whether this is true in humans and its effect on age-related diseases unknown. We utilized levels of human blood plasma proteins originating from specific to measure organ-specific differences living individuals. Using machine learning models, we analysed 11 major estimated organ age reproducibly five independent cohorts encompassing 5,676 adults across the lifespan. discovered nearly...
Recent studies indicate that the adaptive immune system plays a role in Lewy body dementia (LBD). However, mechanism regulating T cell brain homing LBD is unknown. Here, we observed cells adjacent to bodies and dopaminergic neurons postmortem brains. Single-cell RNA sequencing of cerebrospinal fluid (CSF) identified up-regulated expression C-X-C motif chemokine receptor 4 (CXCR4) CD4+ LBD. CSF protein levels CXCR4 ligand, ligand 12 (CXCL12), were associated with neuroaxonal damage...
Cerebrospinal fluid (CSF) contains a tightly regulated immune system. However, knowledge is lacking about how CSF immunity altered with aging or neurodegenerative disease. Here, we performed single-cell RNA sequencing on from 45 cognitively normal subjects ranging 54 to 82 years old. We uncovered an upregulation of lipid transport genes in monocytes age. then compared this cohort 14 impaired subjects. In subjects, downregulation occurred concomitantly cytokine signaling CD8 T cells. Clonal...
Proteomic studies for Alzheimer’s disease (AD) are instrumental in identifying AD pathways but often focus on single tissues and sporadic cases. Here, we present a proteomic study analyzing 1305 proteins brain tissue, cerebrospinal fluid (CSF), plasma from patients with AD, TREM2 risk variant carriers, autosomal dominant (ADAD), healthy individuals. We identified 8 brain, 40 CSF, 9 that were altered individuals replicated these findings several external datasets. signature differentiated...
Abstract Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well Alzheimer’s disease (AD) pathogenesis. We previously reported the MS4A locus key modulator for soluble TREM2 (sTREM2) cerebrospinal fluid (CSF). To identify additional novel genetic modifiers of sTREM2, we performed largest genome-wide association study (GWAS) identified four loci CSF sTREM2 3,350 individuals European ancestry. Through...
The integration of quantitative trait loci (QTL) with disease genome-wide association studies (GWAS) has proven successful at prioritizing candidate genes disease-associated loci. QTL mapping mainly been focused on multi-tissue expression or plasma protein (pQTL). Here we generated the largest-to-date cerebrospinal fluid (CSF) pQTL atlas by analyzing 7,028 proteins in 3,107 samples. We identified 3,373 independent study-wide associations for 1,961 proteins, including 2,448 novel pQTLs which...
To gain insight into how researchers of aging perceive the process they study, we conducted a survey among experts in field. While highlighting some common features aging, exposed broad disagreement on foundational issues. What is aging? causes it? When does it begin? constitutes rejuvenation? Not only was there no consensus these and other core questions, but none questions received majority opinion-even regarding need for itself. Despite many believing understand their understanding...
Abstract Changes in Amyloid-β (A), hyperphosphorylated Tau (T) brain and cerebrospinal fluid (CSF) precedes AD symptoms, making CSF proteome a potential avenue to understand the pathophysiology facilitate reliable diagnostics therapies. Using AT framework three-stage study design (discovery, replication, meta-analysis), we identified 2,173 proteins dysregulated AD, that were further validated third totally independent cohort. Machine learning was implemented create validate highly accurate...
Aging induces region-specific functional decline across the brain. The cerebellum, critical for motor coordination and cognitive function, undergoes significant structural changes with age. molecular mechanisms driving cerebellar aging, particularly role of glia, including microglia, remain poorly understood. Here, we used single-nuclei RNA sequencing (snRNA-seq), microglial bulk RNA-seq, multiplexed error-robust fluorescence in situ hybridization (MERFISH) to characterize transcriptional...
Changes in β-amyloid (Aβ) and hyperphosphorylated tau (T) brain cerebrospinal fluid (CSF) precede Alzheimer's disease (AD) symptoms, making the CSF proteome a potential avenue to understand pathophysiology facilitate reliable diagnostics therapies. Using AT framework three-stage study design (discovery, replication, meta-analysis), we identified 2,173 analytes (2,029 unique proteins) dysregulated AD. Of these, 865 (43%) were previously reported, 1,164 (57%) are novel. The proteins cluster...
Alzheimer disease (AD) is a complex neurodegenerative disorder. Proteomic studies have been instrumental in identifying AD-related proteins present the brain, cerebrospinal fluid, and plasma. This study comprehensively examined 6,905 plasma more than 3,300 well-characterized individuals to identify new proteins, pathways, predictive model for AD. With three-stage analysis (discovery, replication, meta-analysis) we identified 416 (294 novel) associated with clinical AD status findings were...
ABSTRACT Organ-derived plasma protein signatures derived from aptamer arrays track organ-specific aging, disease, and mortality in humans, but the robustness clinical utility of these models their biological underpinnings remain unknown. Here, we estimate age 11 organs 44,526 individuals UK Biobank using an antibody-based proteomics platform to model disease risk. Organ estimates are associated with future onset heart failure (heart HR=1.83), chronic obstructive pulmonary (lung HR=1.39),...
Rates of cognitive decline in Alzheimers disease (AD) are extremely heterogeneous, with ages symptom onset ranging from age 40 to 100 years and conversion mild impairment AD dementia taking 2 20 years. Development biomarkers for amyloid-beta (AB) tau protein aggregates, the hallmark pathologies AD, have improved patient monitoring/stratification drug development, but they still only explain 40% variance (CI) AD. To discover additional molecular drivers dementia, we perform cerebrospinal...
Abstract Background Cerebrospinal fluid (CSF) provides basic mechanical and immunological protection to the brain. Historically, analysis of CSF has focused on protein changes, yet recent studies have shed light cellular alterations. Evidence now exists for involvement intrathecal T cells in pathobiology neurodegenerative diseases. However, a standardized method long-term preservation immune is lacking. Further, functional role their cognate antigens diseases are largely unknown. Results We...
Abstract Background Changes in Amyloid‐β (A) and hyperphosphorylated Tau (T) the brain cerebrospinal fluid (CSF) precedes AD symptoms, making CSF proteome a potential avenue to understand disease pathophysiology facilitate reliable diagnostics therapies. Method We used Somascan assay for measuring protein levels of 7,029 analytes 2,286 participants from four different cohorts. employed three‐stage analytical approach (discovery, replication, meta‐analysis). Firstly, discovery was performed...
Abstract Background Motoric Cognitive Risk (MCR) syndrome is a predementia characterized by slow gait and subjective cognitive concerns. Individuals with MCR are at high risk of transitioning to both Alzheimer's disease (AD) vascular dementia. With chronological age, the incidence increases cases exhibit higher prevalence age‐associated diseases. Biological age reflects an individual's accumulated physiological condition captured changes epigenetic (DNA methylation) as well proteomic levels...
Abstract Background The buildup of brain amyloid‐beta and tau protein aggregates do not sufficiently explain the heterogeneity in cognitive impairment Alzheimer’s disease (AD). Method To elucidate drivers impairment, we measure levels 7,000 proteins, addition to amyloid‐beta‐42 (Ab42) phospho‐tau‐181 (PTau181), from cerebrospinal fluid 2,000 individuals healthy severe dementia. Result We identify synapse proteins as strongest correlates impairment. use machine learning methods derive a...
Abstract Background Cerebrospinal fluid (CSF) is a valuable resource for the study and diagnosis of neurological diseases, but few studies have comprehensively characterized genetic determinants CSF protein levels that may contribute to development disease. These quantitative trait loci (QTL) proven vital identifying candidate genes disease treatment monitoring. Here, we utilize our largest‐to‐date QTL atlas prioritize potentially causal proteins 14 traits examine unique overlapping...
Abstract Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well Alzheimer’s disease (AD) pathogenesis. We previously reported the MS4A locus key modulator for soluble TREM2 (sTREM2) cerebrospinal fluid (CSF). To identify additional novel genetic modifiers of sTREM2, we performed largest genome-wide association study (GWAS) identified four loci CSF sTREM2 3350 individuals European ancestry. Through multi-ethnic...
Abstract Background: Cerebrospinal fluid (CSF) provides basic mechanical and immunological protection to the brain. Historically, analysis of CSF has focused on protein changes, yet recent studies have shed light cellular alterations. Evidence now exists for involvement intrathecal T cells in pathobiology neurodegenerative diseases. However, a standardized method long-term preservation immune is lacking. Further, functional role their cognate antigens diseases are largely unknown. Results:...