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Open AccessABCA7 deficiency causes neuronal dysregulation by altering mitochondrial lipid metabolism
ABCA7 loss-of-function variants are associated with increased risk of Alzheimer’s disease (AD). Using ABCA7 knockout human iPSC models generated with CRISPR/Cas9, we investigated the impacts of ABCA7 deficiency o...
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Article
Cell-autonomous effects of APOE4 in restricting microglial response in brain homeostasis and Alzheimer’s disease
Microglial involvement in Alzheimer’s disease (AD) pathology has emerged as a risk-determining pathogenic event. While apolipoprotein E (APOE) is known to modify AD risk, it remains unclear how microglial apoE im...
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Open AccessDeconvolution reveals cell-type-specific transcriptomic changes in the aging mouse brain
Mounting evidence highlights the crucial role of aging in the pathogenesis of Alzheimer's disease (AD). We have previously explored human apoE-targeted replacement mice across different ages and identified dis...
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Open AccessAPOE deficiency impacts neural differentiation and cholesterol biosynthesis in human iPSC-derived cerebral organoids
The apolipoprotein E (APOE) gene is the strongest genetic risk factor for Alzheimer’s disease (AD); however, how it modulates brain homeostasis is not clear. The apoE protein is a major lipid carrier in the brain...
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Article
Suppression of Wnt/β-Catenin Signaling Is Associated with Downregulation of Wnt1, PORCN, and Rspo2 in Alzheimer’s Disease
Wnt and R-spondin (Rspo) proteins are two major types of endogenous Wnt/β-catenin signaling agonists. While Wnt/β-catenin signaling is greatly diminished in Alzheimer’s disease (AD), it remains to be elucidate...
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Article
Peripheral apoE4 enhances Alzheimer’s pathology and impairs cognition by compromising cerebrovascular function
The ε4 allele of the apolipoprotein E (APOE) gene, a genetic risk factor for Alzheimer’s disease, is abundantly expressed in both the brain and periphery. Here, we present evidence that peripheral apoE isoforms, ...
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Correction to: Apolipoprotein E regulates lipid metabolism and α‑synuclein pathology in human iPSC‑derived cerebral organoids
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Open AccessApolipoprotein E regulates lipid metabolism and α-synuclein pathology in human iPSC-derived cerebral organoids
APOE4 is a strong genetic risk factor for Alzheimer’s disease and Dementia with Lewy bodies; however, how its expression impacts pathogenic pathways in a human-relevant system is not clear. Here using human iPSC-...
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Open AccessAuthor Correction: APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer’s disease patient iPSC-derived cerebral organoids
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Open AccessAPOE4 exacerbates synapse loss and neurodegeneration in Alzheimer’s disease patient iPSC-derived cerebral organoids
APOE4 is the strongest genetic risk factor associated with late-onset Alzheimer’s disease (AD). To address the underlying mechanism, we develop cerebral organoid models using induced pluripotent stem cells (iPSCs...
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Article
Open AccessExtensive transcriptomic study emphasizes importance of vesicular transport in C9orf72 expansion carriers
The majority of the clinico-pathological variability observed in patients harboring a repeat expansion in the C9orf72-SMCR8 complex subunit (C9orf72) remains unexplained. This expansion, which represents the most...
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Article
Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD
Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) represents the most common pathological subtype of FTLD. We established the international FTLD-TDP whole-...
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Article
Open AccessTMEM106B haplotypes have distinct gene expression patterns in aged brain
Single nucleotide polymorphisms (SNPs) inherited as one of two common haplotypes at the transmembrane protein 106B (TMEM106B) locus are associated with the risk of multiple neurodegenerative diseases, including f...
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Article
Open AccessIdentification of missing variants by combining multiple analytic pipelines
After decades of identifying risk factors using array-based genome-wide association studies (GWAS), genetic research of complex diseases has shifted to sequencing-based rare variants discovery. This requires l...
