Publications by authors named "A B Sigalov"

Background: Glial cells exhibit distinct transcriptional responses to β-amyloid pathology in Alzheimer's disease (AD). While sophisticated single-cell based methods have revealed heterogeneous glial subpopulations in the human AD brain, the histological localization of these multicellular responses to AD pathology has not been fully characterized due to the loss of spatial information. Here, we combined spatial transcriptomics (ST) with immunohistochemistry to explore the molecular mechanisms in the neuritic plaque niche.

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TREM-1 and TREM-2 as Therapeutic Targets: Clinical Challenges and Perspectives.

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Article Synopsis
  • Single-nucleus transcriptomic studies have identified specific glial cell states linked to Alzheimer's disease but lack context from the actual structure of the human neocortex.
  • This study used an unbiased analytic strategy to analyze spatially-registered transcriptomic data, finding that certain genes, including metallothioneins, are altered near amyloid plaques.
  • Validation through immunofluorescence showed that a reactive astrocyte subtype, Ast.5, is involved in the environment around these plaques, indicating its potential role in the disease process.
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Systemic sclerosis (SSc) is characterized by immune system failure, vascular insult, autoimmunity, and tissue fibrosis. TGF-β is a crucial mediator of persistent myofibroblast activation and aberrant extracellular matrix production in SSc. The factors responsible for this are unknown.

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Article Synopsis
  • Researchers created a comprehensive cell atlas of the aging brain by analyzing 1.65 million single-nucleus RNA sequences from older adults, revealing specific cell types linked to Alzheimer’s disease (AD).
  • They discovered two distinct microglial subpopulations involved in the progression of amyloid-β and tau proteinopathies, as well as an astrocyte subpopulation linked to cognitive decline.
  • Using a new methodology called BEYOND, the study identified two different pathways of brain aging, which helps in developing personalized therapies targeting specific cellular communities related to AD and other forms of brain aging.
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