Featured Publications
The VCAM1–ApoE pathway directs microglial chemotaxis and alleviates Alzheimer’s disease pathology
Lau S, Wu W, Wong H, Ouyang L, Qiao Y, Xu J, Lau J, Wong C, Jiang Y, Holtzman D, Fu A, Ip N. The VCAM1–ApoE pathway directs microglial chemotaxis and alleviates Alzheimer’s disease pathology. Nature Aging 2023, 3: 1219-1236. PMID: 37735240, PMCID: PMC10570140, DOI: 10.1038/s43587-023-00491-1.Peer-Reviewed Original ResearchConceptsDanger-associated molecular patternsAlzheimer's diseaseMicroglial chemotaxisAmeliorate AD pathologyDisease pathologyAlzheimer's disease pathologyAmyloid-betaFunctional screeningPlaque-associatedMicroglial clearanceAD pathologyExtrinsic signalsPhagocytic clearanceExacerbate disease pathologyMolecular patternsIL-33ChemotaxisMicroglial functionAlzheimerVCAM1Interleukin-33Higher cerebrospinal fluid levelsApoPathwayMicrogliaAn IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE‐ε4 in Alzheimer’s disease
JIANG Y, Zhou X, Wong H, Li O, Ip F, Chau V, Lau S, Wu W, Wong D, Seo H, Fu W, Lai N, Chen Y, Chen Y, Tong E, Mok V, Kwok T, Mok K, Shoai M, Lehallier B, Moran‐Losada P, O’Brien E, Porter T, Laws S, Hardy J, Wyss‐Coray T, Masters C, Fu A, Ip N, Initiative A. An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE‐ε4 in Alzheimer’s disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.064428.Peer-Reviewed Original ResearchGenome-wide association studiesGenetic regulationAlzheimer's diseaseGenome-wide association study analysisGenetic variantsPathogenesis of Alzheimer's diseaseAD risk genesDisease-causing roleAPOE-e4 carriersAssociation studiesGenetic variationAmyloid-betaRisk genesMicroglial clearanceBrains of patientsBackground genetic factorsAD therapySevere neurodegenerationMicroglial dysfunctionAb accumulationMicroglial functionDecoy receptorGenetic factorsAPOE-e4IL1RL1IL-33-PU.1 Transcriptome Reprogramming Drives Functional State Transition and Clearance Activity of Microglia in Alzheimer’s Disease
Lau S, Chen C, Fu W, Qu J, Cheung T, Fu A, Ip N. IL-33-PU.1 Transcriptome Reprogramming Drives Functional State Transition and Clearance Activity of Microglia in Alzheimer’s Disease. Cell Reports 2020, 31: 107530. PMID: 32320664, DOI: 10.1016/j.celrep.2020.107530.Peer-Reviewed Original ResearchConceptsTranscriptome profilingAlzheimer's diseaseTranscription factor bindingSignature genesMicroglial state transitionChromatin accessibilityFactor bindingTranscriptome reprogrammingClearance activityBeta-amyloidTranscriptomeAD pathologyMicroglial transcriptomeTranscriptional pathwaysMajor histocompatibility complex classMicroglial subpopulationsTranscriptomic signaturesEnhanced phagocytic activityMicroglial functionHistocompatibility complex classPhagocytic activityAlzheimerInterleukin (IL)-33Activation of microgliaChromatin
2023
Receptor–ligand interaction controls microglial chemotaxis and amelioration of Alzheimer's disease pathology
Lau S, Fu A, Ip N. Receptor–ligand interaction controls microglial chemotaxis and amelioration of Alzheimer's disease pathology. Journal Of Neurochemistry 2023, 166: 891-903. PMID: 37603311, DOI: 10.1111/jnc.15933.Peer-Reviewed Original ResearchConceptsDanger-associated molecular patternsMicroglial chemotaxisAD pathogenesisAlzheimer's diseaseMicroglial functionRepertoire of surface receptorsHyperphosphorylated tauAlzheimer's disease pathologyAmyloid-betaMolecular machineryMicroglial receptorsReceptor-ligand interactionsPhagocytic clearanceReceptor-ligand axisMolecular patternsSurface receptorsFunctional transitionDisease pathologyChemotaxisBrain homeostasisAberrant synaptic pruningClearance activityCritical stepsReceptorsAmyloid
2021
Cytokine signaling convergence regulates the microglial state transition in Alzheimer’s disease
Lau S, Fu A, Ip N. Cytokine signaling convergence regulates the microglial state transition in Alzheimer’s disease. Cellular And Molecular Life Sciences 2021, 78: 4703-4712. PMID: 33847763, PMCID: PMC8195901, DOI: 10.1007/s00018-021-03810-0.Peer-Reviewed Original ResearchConceptsMicroglial state transitionCytokine signaling pathwaysDanger-associated molecular patternsAlzheimer's diseaseSignaling pathwayPathogenesis of Alzheimer's diseaseAD therapeutic developmentTherapeutic developmentHyperphosphorylated tauBeta-amyloidGenetic analysisAD pathologyCytokine signalingMolecular basisAD progressionMolecular patternsMicroglial dysfunctionSignal convergenceMicroglial responseMicroglial functionStimulated microgliaFunctional stateActive statePathwayChronic activation