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Single-cell transcriptomic analysis of Alzheimer’s disease
Open accessAbstract
Alzheimer’s disease is a pervasive neurodegenerative disorder, the molecular complexity of which remains poorly understood. Here, we analysed 80,660 single-nucleus transcriptomes from the prefrontal cortex of 48 individuals with varying degrees of Alzheimer’s disease pathology. Across six major brain cell types, we identified transcriptionally distinct subpopulations, including those associated with pathology and characterized by regulators of myelination, inflammation, and neuron survival. The strongest disease-associated changes appeared early in pathological progression and were highly cell-type specific, whereas genes upregulated at late stages were common across cell types and primarily involved in the global stress response. Notably, we found that female cells were overrepresented in disease-associated subpopulations, and that transcriptional responses were substantially different between sexes in several cell types, including oligodendrocytes. Overall, myelination-related processes were recurrently perturbed in multiple cell types, suggesting that myelination has a key role in Alzheimer’s disease pathophysiology. Our single-cell transcriptomic resource provides a blueprint for interrogating the molecular and cellular basis of Alzheimer’s disease. Single-cell transcriptomics from 48 individuals with varying degrees of Alzheimer’s disease pathology demonstrates that gene-expression changes in Alzheimer’s disease are both cell-type specific and shared, and that transcriptional responses show sexual dimorphism.
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“snRNA-seq analyses of human brain samples have failed to detect a consistent microglial activation signature in Alzheimer’s disease.”
From Single-Nucleus RNA-Seq Is Not Suitable for Detection of Microglial Activation Genes in Humans (2020) · cites this paper as Mathys et al., 2019
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“Other studies have also found that microglial expression, in general, is particularly underrepresented in bulk transcriptomes, relative to that of other brain cell types (8,42) .”
From Single cell transcriptome profiling of the human alcohol-dependent brain (2020) · cites this paper as [8]
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“These opposing states are accompanied by broad changes in gene expression12–17, suggesting that defined transcriptional programs in microglia may govern their neuroprotective or neurotoxic functions.”
From Lymphoid gene expression supports neuroprotective microglia function (2025) · cites this paper as [14]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Microarrays and bulk RNA-Seq are scalable and cost-effective but lack single-cell resolution.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [118]
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In the citing paper
“Single-cell and single-nucleus methods deliver high granularity but require significant technical and computational resources.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [118]
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“This level of resolution is essential, as epigenetic profiles in glial cells may differ substantially from those in neurons and may play critical roles in processes such as amyloid plaque deposition and neuroinflammation118.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [118]
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In the citing paper
“This technique has revealed distinct microglial and astrocytic subpopulations, such as disease-associated microglia (DAM) and reactive astrocytes, which are involved in plaque clearance, neuroinflammation, and synaptic modulation118,162, 163, 164.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [118]
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In the citing paper
“Recent advances in single‐cell RNA sequencing and spatial transcriptomics (ST) have transformed our understanding of cellular heterogeneity in AD by revealing disease‐associated cell states and spatially localized inflammatory responses.”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“is accompanied by localized cellular responses involving microglial activation, astrocytic reactivity, neuronal stress, and myelin disruption”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [6]
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In the citing paper
“In AD, spatial transcriptomics and single‐cell techniques have revealed plaque‐associated transcriptional niches and cell‐state changes in situ. 6 , 8”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“ST revealed increased microglial and astrocytic gene expression and decreased oligodendrocyte‐ and neuron‐associated signatures, consistent with previous immunohistochemical and transcriptomic studies. 6 , 8 , 77 , 78”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [6]
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In the citing paper
“ST identified upregulation of microglia‐associated genes and downregulation of oligodendrocyte‐associated genes, corresponding to reported enrichment of immune‐response, oxidative‐stress, lysosomal‐function, and myelination pathways. 6 , 8”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [6]
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In the citing paper
“Insight into APOE4-mediated pathogenesis is complicated by the fact that APOE is a soluble factor expressed by many cell types12,13.”
From APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes (2022) · cites this paper as [12]
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In the citing paper
“The study identified 28 DAM genes as marker genes of the Mic1 response cluster (shown in orange in Figure 2F); however, most DAM genes were not identified as activation genes using their snRNA-seq protocol (purple in Figure 2F).”
From Single-Nucleus RNA-Seq Is Not Suitable for Detection of Microglial Activation Genes in Humans (2020) · cites this paper as Mathys et al., 2019
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“Strikingly, we observed ~2.5 times more DEGs in women than in men, consistent with other recently published work (Mathys et al., 2019).”
From Meta-Analysis of the Alzheimer’s Disease Human Brain Transcriptome and Functional Dissection in Mouse Models (2020) · cites this paper as Mathys et al., 2019
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In the citing paper
“but our sample sizes are similar to those reported in previous publications5–14”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“resulting in over 100,000 astrocyte nuclei in each brain region with ≈6,000 average total number of reads and ≈2,500 average total number of genes detected, which is orders of magnitude higher than previous studies9–15”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the CNS, APOE is produced predominantly by astrocytes, although it can also be produced by reactive microglia and, to a lesser extent, stressed neurons and other glial cells96,97.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [97]
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In the citing paper
“We then replicate this observation by repurposing DLPFC single nucleus RNA sequencing data generated from an independent set of MAP subjects9.”
From Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease (2020) · cites this paper as [9]
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In the citing paper
“A recent publication9 generated single-nucleus RNA-seq data from dorsolateral prefrontal cortex in 48 donors (comprising subsets of donors with and without diagnoses of Alzheimer’s disease) from the ROSMAP cohort”
From Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease (2020) · cites this paper as [9]
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In the citing paper
“AD DEGs were consistent with published results both for region-specific DEGs and for DEGs computed jointly over all regions for multiple AD variables, and were further corroborated by comparisons with various independent studies11,12,15,19,47–53”
From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [12]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In addition, microglial functions vary across different ages, disease pathologies, and between sexes10–16.”
From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“which has been shown in animal models and human populations113–115.”
From GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau (2025) · cites this paper as [113]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The research found apolipoprotein E transcripts to be significantly upregulated in AD-associated microglia [88,89].”
From The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders (2023) · cites this paper as [89]
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In the citing paper
“In brain tissue from human AD patients, microglia display the morphology (Heppner et al., 2015) and gene expression profile (Gjoneska et al., 2015; Mathys et al., 2019) characteristic of an activated cell state and cluster around β-amyloid plaques.”
From A novel molecular class that recruits HDAC/MECP2 complexes to PU.1 motifs reduces neuroinflammation (2023) · cites this paper as Mathys et al., 2019
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In the citing paper
“although the mouse DAM transcriptome profile may not be fully present in AD brain, as human microglia show a distinct AD-related gene signature (Jaitin et al., 2019; Mathys et al., 2019).”
From Alzheimer's-associated PU.1 expression levels regulate microglial inflammatory response (2021) · cites this paper as Mathys et al., 2019
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“The maturation of single-cell technologies now enables large-scale comparisons of cell states within complex tissues, thus providing the appropriate resolution to dissect cell-type-specific responses to perturbation5,6.”
From Confronting false discoveries in single-cell differential expression (2021) · cites this paper as [6]
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In the citing paper
“Within our compendium, we identified a total of fourteen studies with control groups that included six or more samples5,6,15,49–59.”
From Confronting false discoveries in single-cell differential expression (2021) · cites this paper as [6]
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In the citing paper
“Single-nucleus RNA sequencing (snRNA-seq) data on postmortem samples from AD patients and on samples from AD mice model also revealed that the expression of TREM2 was increased in AD pathology.164,213,214”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [164]
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In the citing paper
“RNA-seq studies using human AD autopsy samples have identified myelin-related transcripts among the top altered gene clusters in patients with AD35,46.”
From Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease (2023) · cites this paper as [46]
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In the citing paper
“Recently, transcriptomic studies have shown changes not only in microglia and astrocytes but also in oligodendrocytes, the myelinating cells of the central nervous system, in both human AD tissue [5,6]”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“Human single nucleus RNA sequencing data from Mathys and colleagues [5] and Lake and colleagues [12] were obtained from The Myeloid Landscape 2 portal (http://research-pub.gene.com/BrainMyeloidLandscape) [70].”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [5]
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In the citing paper
“myelin alterations have been implicated in AD7–9”
From Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice (2024) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“Our previous single-cell analysis uncovered AD-associated oligodendrocyte subpopulations highlighting a role of myelin-related processes in AD pathogenesis12, consistent with reports of hypomyelination and white matter changes in AD23,24.”
From APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes (2022) · cites this paper as [12]
The cited source says what the claim attributes to it.
In the citing paper
“We performed consensus co-expression network analysis of microglia from three Alzheimer’s disease (AD) snRNA-seq studies,10,11,12 yielding multiple gene modules corresponding to disease-associated microglia and polygenic risk of AD.”
From hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data (2023) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“Next, we performed consensus co-expression network analysis using microglia integrated from three human AD snRNA-seq datasets,10,11,12 identifying four consensus modules (Figure 6C; Data S1).”
From hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data (2023) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“Markers of this response (referred to by Mathys et al., 2019 as “Mic1”) had a NES score of −2.14 (padj = 3.6e-05), indicating that they were depleted in nuclei (Figure 2C).”
From Single-Nucleus RNA-Seq Is Not Suitable for Detection of Microglial Activation Genes in Humans (2020) · cites this paper as Mathys et al., 2019
The cited source says what the claim attributes to it.
In the citing paper
“Our results are consistent with prior observations in both mice (Jiao et al., 2016) and humans (Altmann et al., 2014; Li and Singh, 2014; Mayeux and Stern, 2012; Mathys et al., 2019; Sala Frigerio et al., 2019).”
From Meta-Analysis of the Alzheimer’s Disease Human Brain Transcriptome and Functional Dissection in Mouse Models (2020) · cites this paper as Mathys et al., 2019
The cited source says what the claim attributes to it.
In the citing paper
“APOE is one such lipid-related AD risk gene, which is highly upregulated in human microglia in AD3”
From APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia (2024) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“Indeed, APOE expression in microglia is increased in the brains of AD patients and is a marker for disease‐associated microglia (DAM). 52 , 53”
From Deletion of miR-33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice (2024) · cites this paper as [52]
The cited source says what the claim attributes to it.
In the citing paper
“Previous studies described AD-associated molecular and cellular changes5–15; however, cross-study comparisons are challenging without common cell annotations.”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“To corroborate the results, we harmonized snRNA-seq data and associated donor metadata from the PFC from ten additional AD studies spanning 707 donors5–14.”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“ScRNAseq and snRNAseq are becoming established as valuable tools to gain insight into basal94 and reactive-astrocyte heterogeneity (Fig. 1e)40,78,95.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [95]
The cited source says what the claim attributes to it.
In the citing paper
“our sample sizes are similar to those reported in previous publications9–17”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“APOE is greatly upregulated in human AD microglia (HAM) from human AD brains”
From ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease (2022) · cites this paper as Mathys et al 2019
The cited source says what the claim attributes to it.
In the citing paper
“Interestingly, the expression of ApoE, which regulates lipid homeostasis, is downregulated in astrocytes in AD (9, 10)”
From Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes (2024) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“apolipoprotein E (ApoE), a major mediator of lipid transport in the brain, is downregulated in astrocytes in AD (9, 10)”
From Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes (2024) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“Recently, studies of single nucleus RNA sequencing from human brain reported either no detectable population structure in microglial cells7,8 or a maximum of four transcriptionally distinct microglial subsets9.”
From Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease (2020) · cites this paper as [9]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Spatial transcriptomics adds a critical spatial dimension but may trade off resolution or transcriptomic depth114,118,162,166.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [118]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Machine learning applied to metabolomic data can also identify how microbial metabolites affect neuronal health and inflammatory status118.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [118]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“altering tissue microstructure and metal homeostasis”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [6]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“We found that, apart from PSEN2 (which is not essential for gamma secretase function when PSEN1 is present [13]), oligodendrocytes had elevated expression of all of these genes (Fig 1A–1D).”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [5]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“RNA sequencing (RNAseq) of the prefrontal cortex (PFC) of the P301S human Tau transgenic mouse model of dementia has identified Serum and Glucocorticoid-regulated Kinase-1 (Sgk1) as one of the top-ranking upregulated genes [10].”
From Elevated SGK1 increases Tau phosphorylation and microtubule instability in Alzheimer’s patient-derived cortical neurons (2026) · cites this paper as [11]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“We next analyzed recent snRNA-seq datasets of AD patients from two independent studies28, 33, both showing a specific upregulation of PLXNB1 in astrocytes but not other cell types in human AD brains (Fig. 2B).”
From Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease (2024) · cites this paper as [28]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“single nucleus (sn) RNA-sequencing (-seq) identified PLXNB1 as one of the top induced genes in astrocytes in early stages of AD28.”
From Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease (2024) · cites this paper as [28]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“may have confounded previous studies that compared only control and severe AD donors or grouped late- and end-stage donors (Braak stage V/VI) together9–15”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [9]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Although some brain regions relevant to AD have been studied individually at scale or jointly in samples from a few individuals8–16, a comprehensive molecular characterization of region-specific differences in AD is currently lacking”
From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [12]
Experimental — accuracy not yet measuredIn the citing paper
“In addition to the downregulation of genes involved in synaptic transmission and synapse organization, there is also prominent upregulation of genes involved in cell stress, immune response activation and cell death in PFC of AD patients 257–259.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [257]
In the citing paper
“Single nuclei analysis of human AD brain specimens has revealed a microglial transcriptional response that partially recapitulates the mouse DAM signature along with perturbation of oligodendrocytes and myelination that is gender-dependent20.”
From Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease (2020) · cites this paper as [20]
In the citing paper
“Several cell type-specific upregulated genes identified by Mathys et al., including MHC class II and APOE in microglia and QDPR, CA2, and SLC38A2 in oligodendrocytes, were also upregulated in our AD samples.”
From Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease (2020) · cites this paper as [20]
In the citing paper
“Our human data are partially concordant with a recent study examining human AD and control samples by snRNA-seq20.”
From Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease (2020) · cites this paper as [20]
In the citing paper
“In line with this, single cell transcriptomic profiles in AD postmortem brains suggested altered molecular profiles in oligodendrocytes24.”
From A computational tool (H-MAGMA) for improved prediction of brain-disorder risk genes by incorporating brain chromatin interaction profiles (2020) · cites this paper as [24]
In the citing paper
“Cell-type specific DEG in AD postmortem brains was obtained from Mathys et al., 201924.”
From A computational tool (H-MAGMA) for improved prediction of brain-disorder risk genes by incorporating brain chromatin interaction profiles (2020) · cites this paper as [24]
In the citing paper
“OLIG associates strongly (odds ratio: 4.06) with the human AD-associated oligodendrocytes Oli0 (Mathys et al. , 2019) (Figure S3E).”
From Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease (2020) · cites this paper as Mathys et al., 2019
In the citing paper
“We evaluated whether the PIGs could be identified in a human dataset (Mathys et al., 2019). Among the 41 cellular subpopulations (Mathys et al. , 2019), the highest association of PIGs is with an AD-associated microglial signature (Mic1, odds ratio: 4.28; Figure S3E).”
From Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease (2020) · cites this paper as Mathys et al., 2019
In the citing paper
“However, single cell transcriptomic experiments have recently shown a positive correlation of AD pathology with increased expression of genes responsible for myelination in oligodendrocytes in AD patients (Grubman et al. , 2019; Mathys et al. , 2019).”
From Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease (2020) · cites this paper as Mathys et al., 2019
In the citing paper
“This subpopulation was marked by expression of microglial activation genes previously associated with human disease4,5, such as complement C1QC, CD74, FTL and FTH1, and downregulation of the homeostatic markers including P2RY12”
From Dysregulation of brain and choroid plexus cell types in severe COVID-19 (2021) · cites this paper as [5]
In the citing paper
“Microglial subclusters that are associated with disease have been identified for various neurodegenerative diseases4,5.”
From Dysregulation of brain and choroid plexus cell types in severe COVID-19 (2021) · cites this paper as [5]
In the citing paper
“For example, we showed that the dysregulated pathways in neurons and oligodendrocytes are associated with synaptic signaling and myelination, respectively; these findings are similar to those in previous studies despite variations in study cohorts, brain regions, sample preparation, and sequencing protocols (12, 13, 23).”
From Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease (2020) · cites this paper as [12]
In the citing paper
“We found 273 cell type-specific DEGs in common between the two datasets, including 53 in astrocytes, 97 in excitatory neurons, 24 in inhibitory neurons, 13 in microglia, and 86 in oligodendrocytes (SI Appendix, Fig. S4 A, B, D, E, G, H, J, K, M, and N).”
From Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease (2020) · cites this paper as [12]
In the citing paper
“However, such changes were not observed in previous snRNA-seq studies (12, 13), possibly due to a lower proportion of endothelial nuclei being sampled.”
From Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease (2020) · cites this paper as [12]
In the citing paper
“However, the proportion of endothelial cells in the previous dataset was low, rendering it unsuitable for validating our findings in endothelial cells.”
From Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease (2020) · cites this paper as [12]
In the citing paper
“To exclude potential dead cells and cell debris from the dataset, we filtered out nuclei with ≤200 genes, ≥20,000 unique molecular identifiers, or ≥20% mitochondrial genes as described in several previous snRNA-seq studies (12, 13, 22, 53).”
From Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease (2020) · cites this paper as [12]
In the citing paper
“We removed nuclei with high mitochondria gene expression following a previously proposed dynamic model61.”
From Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy (2021) · cites this paper as [61]
In the citing paper
“Single nuclear transcriptomic techniques have recently been applied to human AD brain specimens and have identified microglial subtypes with increased Apoe expression but have failed to identify DAM or MGnD subpopulations similar to what has been seen in the mouse brain (Mathys et al., 2019).”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Mathys et al., 2019
In the citing paper
“By performing snRNA-seq in >80,000 single nuclei from 48 individuals with Alzheimer’s disease (AD) pathology (Mathys et al., 2019), many more differentially expressed (DE) genes were detected in individual cell types than bulk tissue.”
From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Mathys et al., 2019
In the citing paper
“In particular, gene dysregulation in glial cells was detected in snRNA-seq, but not bulk RNA-seq, due to the relatively low contribution of glia to the total RNA in the tissue.”
From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Mathys et al., 2019
In the citing paper
“Transcriptomic signatures of disease can be studied by snRNA-seq applied to post-mortem brain tissue from patients.”
From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Mathys et al., 2019
In the citing paper
“Notably, they were enriched for genes that are upregulated in microglia from postmortem AD brain50 (Fig. 4f).”
From Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders (2021) · cites this paper as [50]
In the citing paper
“This is consistent with recent single-cell sequencing studies identifying genetic risk enrichment and gene expression changes within microglia in AD, accompanied by significant gene expression changes in other cells, including astrocytes50–52, which is where we observe epigenetic signature enrichment.”
From Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders (2021) · cites this paper as [50]
In the citing paper
“We then annotated the clusters using the following markers of major brain cell types that are consistently detected in single cell/nucleus transcriptomics studies (7,8,20,23,24) : excitatory neurons, astrocytes, oligodendrocytes, inhibitory/GABAergic neurons, oligodendrocyte progenitor cells (OPCs), microglia, and endothelial cells ( Fig 1C-D ).”
From Single cell transcriptome profiling of the human alcohol-dependent brain (2020) · cites this paper as [8]
In the citing paper
“Proportions of the different cell types were comparable to other snRNA-seq studies (8,23) with neurons (particularly excitatory neurons) being over-represented relative to non-neuronal cell types ( Fig S2 ).”
From Single cell transcriptome profiling of the human alcohol-dependent brain (2020) · cites this paper as [8]
In the citing paper
“Bulk and scRNA-seq studies often exclude non-coding RNAs from their analyses (3,8,35) .”
From Single cell transcriptome profiling of the human alcohol-dependent brain (2020) · cites this paper as [8]
In the citing paper
“Similar to iNs, iPSC-iN cultures contained vGlut1+ and GABA+ neurons and expressed marker genes for both subtypes, and both showed the highest similarity to cortical excitatory neurons from single-cell RNA-seq (scRNA-seq) data (Figure 7D; Figure S5; Mathys et al., 2019).”
From Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer’s patients (2021) · cites this paper as Mathys et al., 2019
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Citations
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Metadata
- Authors
- Mathys, H., Davila-Velderrain, J., Peng, Z., Gao, F., Mohammadi, S., Young, J. Z., Menon, M., He, L., Abdurrob, F., Jiang, X., Martorell, A. J., Ransohoff, R. M., Hafler, B. P., Bennett, D. A., Kellis, M., & Tsai, L.-H.
- Affiliations
- Massachusetts Institute of Technology (US)
- Broad Institute (US)
- Rush University Medical Center (US)
- Corresponding author
- Kellis, Manolis
- Tsai, Li-Huei
- ORCID
- Venue
- Nature
- Published
- 2019-05-01
- Volume
- 570
- Issue
- 7761
- Pages
- 332-337
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6865822
- OpenAlex
- W2942678593
- Semantic Scholar
- 2a3f8208aadb36d1c90d869252fa5f052bace572
- Cited by
- 2,568
- References
- 61
- Citations by year
- 2026: 343 · 2025: 403 · 2024: 414 · 2023: 371 · 2022: 375 · 2021: 368 · 2020: 244 · 2019: 45
- FWCI
- 87.80
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-06-17)
- Open access
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (151885)
- National Institute on Aging (R01AG017917, R01AG058002, R01AG062335, RF1AG054012, U01AG046152, R01AG015819, P30AG010161, RF1AG062377, R01AG046174, RF1AG054321, RF1AG057473, P30AG062421)
- National Institute of Mental Health (U01MH119509, R01MH109978)
- National Human Genome Research Institute (R01HG008155)
- National Eye Institute (K08EY026652)
- National Institute of Neurological Disorders and Stroke (U01NS110453)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, single-nucleus transcriptomics, prefrontal cortex, cell type-specific gene expression, myelination, oligodendrocytes, sex differences, inflammation, neuronal survival, stress response, disease progression, neurodegeneration
- MeSH terms
- Aging, Alzheimer Disease, Female, Humans, Male, Organ Specificity, RNA, Messenger, Sex Characteristics, Prefrontal Cortex, Sequence Analysis, RNA, Disease Progression, Gene Expression Profiling, Single-Cell Analysis, Transcriptome
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