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Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer's disease.
Otero-Garcia, Marcos; Mahajani, Sameehan U; Wakhloo, Debia; Tang, Weijing; Xue, Yue-Qiang; Morabito, Samuel; Pan, Jie; Oberhauser, Jane; Madira, Angela E; Shakouri, Tamara; Deng, Yongning; Allison, Thomas; He, Zihuai; Lowry, William E; Kawaguchi, Riki; Swarup, Vivek; Cobos, Inma.
Afiliação
  • Otero-Garcia M; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Mahajani SU; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Wakhloo D; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Tang W; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Xue YQ; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Morabito S; Mathematical, Computational and Systems Biology Program, University of California, Irvine, CA 92697, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, USA.
  • Pan J; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Oberhauser J; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Madira AE; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Shakouri T; Department of Pathology, University of California, Los Angeles, CA 90095, USA.
  • Deng Y; Department of Pathology, University of California, Los Angeles, CA 90095, USA; Department of Neurology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • Allison T; Department of Biological Chemistry, University of California, Los Angeles, CA 90095, USA.
  • He Z; Department Neurology and Neurological Sciences and Quantitative Sciences Unit, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
  • Lowry WE; Department of Molecular Cell and Developmental Biology, Broad Center for Regenerative Medicine and Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
  • Kawaguchi R; Department of Psychiatry and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, USA.
  • Swarup V; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, USA; Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA.
  • Cobos I; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: icobos@stanford.edu.
Neuron ; 110(18): 2929-2948.e8, 2022 09 21.
Article em En | MEDLINE | ID: mdl-35882228
ABSTRACT
Tau aggregation in neurofibrillary tangles (NFTs) is closely associated with neurodegeneration and cognitive decline in Alzheimer's disease (AD). However, the molecular signatures that distinguish between aggregation-prone and aggregation-resistant cell states are unknown. We developed methods for the high-throughput isolation and transcriptome profiling of single somas with NFTs from the human AD brain, quantified the susceptibility of 20 neocortical subtypes for NFT formation and death, and identified both shared and cell-type-specific signatures. NFT-bearing neurons shared a marked upregulation of synaptic transmission-related genes, including a core set of 63 genes enriched for synaptic vesicle cycling. Oxidative phosphorylation and mitochondrial dysfunction were highly cell-type dependent. Apoptosis was only modestly enriched, and the susceptibilities of NFT-bearing and NFT-free neurons for death were highly similar. Our analysis suggests that NFTs represent cell-type-specific responses to stress and synaptic dysfunction. We provide a resource for biomarker discovery and the investigation of tau-dependent and tau-independent mechanisms of neurodegeneration.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Emaranhados Neurofibrilares / Doença de Alzheimer Idioma: En Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Emaranhados Neurofibrilares / Doença de Alzheimer Idioma: En Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos