Wayne W. Poon
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View article: The P301L tau mutation alters extracellular vesicle biogenesis in astrocyte and contributes to astrocyte‐mediated tau pathology in a human iPSC‐derived model of tauopathies
The P301L tau mutation alters extracellular vesicle biogenesis in astrocyte and contributes to astrocyte‐mediated tau pathology in a human iPSC‐derived model of tauopathies Open
Background Tauopathies are a group of neurodegenerative disorders which are characterized by the accumulation of abnormal tau protein in the brain. However, the mechanistic understanding of pathogenic tau formation and spread within the br…
View article: The impact of astrocytic NF-κB on healthy and Alzheimer’s disease brains
The impact of astrocytic NF-κB on healthy and Alzheimer’s disease brains Open
Astrocytes play a role in healthy cognitive function and Alzheimer’s disease (AD). The transcriptional factor nuclear factor-κB (NF-κB) drives astrocyte diversity, but the mechanisms are not fully understood. By combining studies in human …
View article: Dissecting the Ability of Siglecs To Antagonize Fcγ Receptors
Dissecting the Ability of Siglecs To Antagonize Fcγ Receptors Open
Fcγ receptors (FcγRs) play key roles in the effector function of IgG, but their inappropriate activation plays a role in several disease etiologies. Therefore, it is critical to better understand how FcγRs are regulated. Numerous studies s…
View article: Interrogating CD33 exon‐2 skipping in iPSC‐derived microglia
Interrogating CD33 exon‐2 skipping in iPSC‐derived microglia Open
Background AD Genome‐wide association studies (AD‐GWAS) of late‐onset AD (LOAD) have identified single nucleotide polymorphisms (SNPs) within genes predominantly expressed in microglia (TREM2, TYROBP, CD33, CR1, PILRA, PLCG2, INPP5D, BIN1,…
View article: Differential Vulnerability of Hippocampal Subfields in Primary Age-Related Tauopathy and Chronic Traumatic Encephalopathy
Differential Vulnerability of Hippocampal Subfields in Primary Age-Related Tauopathy and Chronic Traumatic Encephalopathy Open
Chronic traumatic encephalopathy (CTE) is a tauopathy associated with repetitive mild head impacts characterized by perivascular hyperphosphorylated tau (p-tau) in neurofibrillary tangles (NFTs) and neurites in the depths of the neocortica…
View article: Integrated transcriptome analysis of Huntington’s disease iPSC-derived and mouse astrocytes implicates dysregulated synaptogenesis, actin, and astrocyte maturation
Integrated transcriptome analysis of Huntington’s disease iPSC-derived and mouse astrocytes implicates dysregulated synaptogenesis, actin, and astrocyte maturation Open
Summary Huntington’s disease (HD) is a neurodegenerative disease caused by an expanded CAG repeat within the Huntingtin ( HTT ) gene having dysregulated cellular homeostasis in the central nervous system, particularly in the striatum and c…
View article: Human neural cell type‐specific extracellular vesicle proteome defines disease‐related molecules associated with activated astrocytes in Alzheimer's disease brain
Human neural cell type‐specific extracellular vesicle proteome defines disease‐related molecules associated with activated astrocytes in Alzheimer's disease brain Open
In neurodegenerative diseases, extracellular vesicles (EVs) transfer pathogenic molecules and are consequently involved in disease progression. We have investigated the proteomic profiles of EVs that were isolated from four different human…
View article: Genome-wide association study and functional validation implicates JADE1 in tauopathy
Genome-wide association study and functional validation implicates JADE1 in tauopathy Open
Primary age-related tauopathy (PART) is a neurodegenerative pathology with features distinct from but also overlapping with Alzheimer disease (AD). While both exhibit Alzheimer-type temporal lobe neurofibrillary degeneration alongside amne…
View article: Exosomal tau with seeding activity is released from Alzheimer's disease synapses, and seeding potential is associated with amyloid beta
Exosomal tau with seeding activity is released from Alzheimer's disease synapses, and seeding potential is associated with amyloid beta Open
Synaptic transfer of tau has long been hypothesized from the human pathology pattern and has been demonstrated in vitro and in vivo, but the precise mechanisms remain unclear. Extracellular vesicles such as exosomes have been suggested as …
View article: Genome-wide association study and functional validation implicates JADE1 in tauopathy
Genome-wide association study and functional validation implicates JADE1 in tauopathy Open
Primary age-related tauopathy (PART) is a neurodegenerative tauopathy with features distinct from but also overlapping with Alzheimer disease (AD). While both exhibit Alzheimer-type temporal lobe neurofibrillary degeneration alongside amne…
View article: Early Selective Vulnerability of the CA2 Hippocampal Subfield in Primary Age-Related Tauopathy
Early Selective Vulnerability of the CA2 Hippocampal Subfield in Primary Age-Related Tauopathy Open
Primary age-related tauopathy (PART) is a neurodegenerative entity defined as Alzheimer-type neurofibrillary degeneration primarily affecting the medial temporal lobe with minimal to absent amyloid-β (Aβ) plaque deposition. The extent to w…
View article: Genetic studies of Alzheimer's disease risk implicate clearance of lipid rich debris in myeloid cells
Genetic studies of Alzheimer's disease risk implicate clearance of lipid rich debris in myeloid cells Open
Background Genome‐wide association studies (GWAS) have identified more than forty loci associated with Alzheimer’s disease (AD), but the causal variants, regulatory elements and genes remain largely unknown, impeding a mechanistic understa…
View article: Differential effects of apolipoprotein E on the molecular and cellular phenotypes associated with Alzheimer’s disease in isogenic human iPSC‐derived neurons
Differential effects of apolipoprotein E on the molecular and cellular phenotypes associated with Alzheimer’s disease in isogenic human iPSC‐derived neurons Open
Background Apolipoprotein E4 ( APOE4 ) is an established AD risk gene, while APOE2 is considered protective. Recently, several studies demonstrated that APOE4 can induce AD‐related pathological phenotypes including tau phosphorylation (p‐t…
View article: Integration of Alzheimer’s disease genetics and myeloid genomics reveals novel disease risk mechanisms
Integration of Alzheimer’s disease genetics and myeloid genomics reveals novel disease risk mechanisms Open
Background Genome‐wide association studies (GWAS) have identified more than forty loci associated with Alzheimer’s disease (AD), but the causal variants, regulatory elements and genes remain largely unknown, impeding a mechanistic understa…
View article: Cholesterol and matrisome pathways dysregulated in human <i>APOE</i> ε4 glia
Cholesterol and matrisome pathways dysregulated in human <i>APOE</i> ε4 glia Open
Apolipoprotein E ( APOE ) ε4 is the strongest genetic risk factor for Alzheimer’s disease (AD). Although its association with AD is well-established, the impact of APOE ε4 on human brain cell function remains unclear. Here we investigated …
View article: Integration of Alzheimer’s disease genetics and myeloid genomics reveals novel disease risk mechanisms
Integration of Alzheimer’s disease genetics and myeloid genomics reveals novel disease risk mechanisms Open
Genome-wide association studies (GWAS) have identified more than thirty loci associated with Alzheimer’s disease (AD), but the causal variants, regulatory elements, genes and pathways remain largely unknown thus impeding a mechanistic unde…
View article: P4‐182: NEURONAL AND OLIGODENDROGLIAL EXOSOMAL α‐SYNUCLEIN DISTINGUISHES PARKINSON'S DISEASE FROM MULTIPLE SYSTEM ATROPHY
P4‐182: NEURONAL AND OLIGODENDROGLIAL EXOSOMAL α‐SYNUCLEIN DISTINGUISHES PARKINSON'S DISEASE FROM MULTIPLE SYSTEM ATROPHY Open
Synucleinopathies, including Parkinson's disease (PD), Dementia with Lewy bodies (DLB), and Multiple System Atrophy (MSA) are all characterized by aggregation and deposition of α-synuclein in the brain. Diagnosis of different synucleinopat…
View article: Analysis of shared heritability in common disorders of the brain
Analysis of shared heritability in common disorders of the brain Open
Brainstorming diseases Consistent classification of neuropsychiatric diseases is problematic because it can lead to misunderstanding of etiology. The Brainstorm Consortium examined multiple genome-wide association studies drawn from more t…
View article: Cerebrovascular pathology in Down syndrome and Alzheimer disease
Cerebrovascular pathology in Down syndrome and Alzheimer disease Open
People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD) with age. Typically, by age 40 years, most people with DS have sufficient neuropathology for an AD diagnosis. Interestingly, atherosclerosis and hyperten…
View article: Evaluation of Apolipoprotein E Fragmentation as a Biomarker for Alzheimer’s Disease
Evaluation of Apolipoprotein E Fragmentation as a Biomarker for Alzheimer’s Disease Open
Recent studies have supported a role for the proteolytic cleavage of apolipoprotein E4 (APOE4) as a potential mechanism for the enhanced dementia risk associated with Alzheimer's disease. To determine whether APOE4 fragmentation is correla…
View article: Super‐resolution imaging of subcortical white matter using stochastic optical reconstruction microscopy (STORM) and super‐resolution optical fluctuation imaging (SOFI)
Super‐resolution imaging of subcortical white matter using stochastic optical reconstruction microscopy (STORM) and super‐resolution optical fluctuation imaging (SOFI) Open
Aims The spatial resolution of light microscopy is limited by the wavelength of visible light (the ‘diffraction limit’, approximately 250 nm). Resolution of sub‐cellular structures, smaller than this limit, is possible with super resolutio…