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Irving Medical Center
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TaubCONNECT Research Perspective:
June 2025
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April 2023:
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February 2023:
APOE and Alzheimer's Disease and Related Dementias Risk Among 12,221 Hispanics/Latinos
A Human Brain Map of Mitochondrial Respiratory Capacity and Diversity
ANXA11 Biomolecular Condensates Facilitate Protein-Lipid Phase Coupling on Lysosomal Membranes
Axonal Transport of CHMP2b Is Regulated by Kinesin-Binding Protein and Disrupted by CHMP2bintron5
Sleep Genetics and Cognitive Changes over Time: The Moderating Effect of Age and the Role of Brain
Emerging Roles for Tubulin PTMs in Neuronal Function and Neurodegenerative Disease
Inflammatory Biomarkers Profiles and Cognition Among Older Adults
Synaptic and Cognitive Impairment Associated with L444P Heterozygous Glucocerebrosidase Mutation
Regulation of Synapse Density by Pumilio RNA-Binding Proteins
CD33 and SHP-1/PTPN6 Interaction in Alzheimer's Disease
Cellular Communities Reveal Trajectories of Brain Ageing and Alzheimer's Disease
Epigenetic and Genetic Risk of Alzheimer Disease from Autopsied Brains in two Ethnic Groups
Multi-Omic Analysis of Huntington's Disease Reveals a Compensatory Astrocyte State
Design and Methods of the Early Age-Related Hearing Loss Investigation Randomized Controlled Trial
Updated Safety Results From Phase 3 Lecanemab Study in Early Alzheimer's Disease
The Broken Alzheimer's Disease Genome
Rare Genetic Variation in Fibronectin 1 (FN1) Protects Against APOEε4 in Alzheimer's Disease
Cell Subtype-Specific Effects of Genetic Variation in the Alzheimer's Disease Brain
Diet, Pace of Biological Aging, and Risk of Dementia in the Framingham Heart Study
A Comparative Study of Structural Variant Calling in WGS from Alzheimer's Disease Families
Glucocorticoid Stress Hormones Stimulate Vesicle-Free Tau Secretion and Spreading in the Braint
The Effects of Insufficient Sleep and Adequate Sleep on Cognitive Function in Healthy Adults
ZCCHC17 Modulates Neuronal RNA Splicing and Supports Cognitive Resilience in Alzheimer's Disease
Effects of Lithium on Serum Brain-Derived Neurotrophic Factor in Alzheimer's Patients with Agitation
2023 Taub Institute Grants for Emerging Research (TIGER) Awardees!
Rie1 and Sgn1 Form an RNA-Binding Complex that Enforces the Meiotic Entry Cell Fate Decision
Memory and Language Cognitive Data Harmonization Across the United States and Mexico
Education as a Moderator of Help Seeking Behavior in Subjective Cognitive Decline
Multicellular Communities are Perturbed in the Aging Human Brain and Alzheimer's Disease
The Neuropathological Landscape of Hispanic and non-Hispanic White Decedents with Alzheimer Disease
The Early-Onset Alzheimer's Disease Whole-Genome Sequencing Project: Study Design and Methodology
Polygenic Risk Score Penetrance & Recurrence Risk in Familial Alzheimer Disease
High School Quality is Associated with Cognition 58 Years Later
Glucocorticoid-Driven Mitochondrial Damage Stimulates Tau Pathology
A Global View of the Genetic Basis of Alzheimer Disease
ARIA in Patients Treated with Lecanemab (BAN2401) in a Phase 2 Study in Early Alzheimer's Disease
Microglia Reactivity Entails Microtubule Remodeling from Acentrosomal to Centrosomal Arrays
Genuine Selective Caspase-2 Inhibition with new Irreversible Small Peptidomimetics
Cell Type-Specific Changes Identified by Single-Cell Transcriptomics in Alzheimer's Disease
Brain Aging Among Racially and Ethnically Diverse Middle-Aged and Older Adults
First Place: Neuroproteasome Localization and Dysfunction Modulate Pathology in Alzheimer's Disease
Clearance of an Amyloid-Like Translational Repressor is Governed by 14-3-3 Proteins
Diet Moderates the Effect of Resting State Functional Connectivity on Cognitive Function
Retromer Deficiency in Tauopathy Models Enhances the Truncation and Toxicity of Tau
Progranulin Mutations in Clinical and Neuropathological Alzheimer's Disease
Wolframin is a Novel Regulator of Tau Pathology and Neurodegeneration
Homotypic Fibrillization of TMEM106B Across Diverse Neurodegenerative Diseases
Correlation of Plasma and Neuroimaging Biomarkers in Alzheimer's Disease
Tubulin Tyrosination Regulates Synaptic Function and is Disrupted in Alzheimer's Disease
The Penalty of Stress - Epichaperomes Negatively Reshaping the Brain in Neurodegenerative Disorders
The Neuronal Retromer can Regulate Both Neuronal and Microglial Phenotypes of Alzheimer's Disease
Deep Learning Improves Utility of Tau PET in the Study of Alzheimer's Disease
Age of Onset of Huntington's Disease in Carriers of Reduced Penetrance Alleles
Caspase-9: A Multimodal Therapeutic Target With Diverse Cellular Expression in Human Disease
Midlife Vascular Factors and Prevalence of Mild Cognitive Impairment in Late-Life in Mexico
The Association Between Sex and Risk of Alzheimer's Disease in Adults with Down Syndrome
Marked Mild Cognitive Deficits in Humanized Mouse Model of Alzheimer's-Type Tau Pathology
Rapid ATF4 Depletion Resets Synaptic Responsiveness after cLTP
Polygenic Risk Score for Alzheimer's Disease in Caribbean Hispanics
Recognition Memory and Divergent Cognitive Profiles in Prodromal Genetic Frontotemporal Dementia
The Microtubule Cytoskeleton at the Synapse & The Synaptic Life of Microtubules
Optimizing Subjective Cognitive Decline to Detect Early Cognitive Dysfunction
The AD Tau Core Spontaneously Self-Assembles and Recruits Full-Length Tau to Filaments
Olfactory Impairment is Related to Tau Pathology and Neuroinflammation in Alzheimer's Disease
Pathogenic Role of Delta 2 Tubulin in Bortezomib-Induced Peripheral Neuropathy
 |  | |
| Verena Haage, PhD | Philip L. De Jager, MD, PhD |
Disease-associated microglia (DAM) have been widely implicated in neurodegeneration, yet their precise role and regulatory mechanisms in the human brain remain incompletely defined. To address this, our team from the Taub Institute and the Center for Translational & Computational Neuroimmunology (CTCN), led by first author Dr. Verena Haage, in collaboration with colleagues from the Ludwig Center for Research on Neurodegeneration, developed a pharmacological approach to model human DAM in vitro—work recently published in Brain, Behavior, and Immunity.
Graphical Abstract
Using an in silico screening strategy, we prioritized two HDAC inhibitors, Vorinostat and Entinostat, which reproducibly engage key components of the human DAM transcriptional signature in microglia-like cells. These compounds not only induced expression of canonical DAM markers—including CD9, LPL, and SPP1—but also significantly upregulated MITF, a transcription factor recently proposed as a regulator of DAM-associated programs. Importantly, HDAC inhibitor-treated cells exhibited selective functional changes: enhanced uptake of amyloid β and dextran, reduced phagocytosis of bacterial particles, and attenuation of MCP-1 secretion in response to inflammatory stimuli. These findings were validated across two distinct human microglial model systems: the HMC3 microglia-like cell line and iPSC-derived microglia.
By providing a scalable and reproducible method to induce DAM-like states in human cells, our work advances the experimental toolkit for dissecting DAM biology. Moreover, our results support the emerging view that DAM signatures reflect at least two distinct transcriptional programs, underscoring the complexity of microglial polarization in neurodegenerative disease contexts. This platform offers new opportunities to mechanistically interrogate DAM function and to explore the translational potential of pharmacologically modulating microglial states.
Philip L. De Jager, MD, PhD
Weil-Granat Professor of Neurology(in The Taub Institute)
pld2115@cumc.columbia.edu
Contact Us
630 West 168th Street
P&S Box 16
New York, NY 10032
Phone: 212 305-1818
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Email: taubinstitute@columbia.edu
Brain Donation
Our ability to understand Alzheimer's disease is dependent upon studying brain tissue.
For more information, please contact Donovan Laing at (212) 305-9086 dal2190@cumc.columbia.edu
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