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Cited by 148Alzheimer's disease research and treatmentsSingle-cell and spatial transcriptomicsDementia and Cognitive Impairment Research

Insights into Alzheimer’s disease from single-cell genomic approaches

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Murdock, Mitchell H., Tsai, Li-Huei·2023·Nature Neuroscience
DOI 10.1038/s41593-022-01222-2PMC PMC10155598
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Abstract

Alzheimer's disease (AD) is an age-related disease pathologically defined by the deposition of amyloid plaques and neurofibrillary tangles in the brain parenchyma. Single-cell profiling has shown that Alzheimer's dementia involves the complex interplay of virtually every major brain cell type. Here, we highlight cell-type-specific molecular perturbations in AD. We discuss how genomic information from single cells expands existing paradigms of AD pathogenesis and highlight new opportunities for therapeutic interventions.

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  • Several pathways altered by a short-term E4 to E2 transition are also perturbed across 17 large-scale human AD snRNA-seq studies.

    “several pathways altered by a short-term E4 to E2 transition were cellular pathways that are also perturbed across 17 large-scale human AD snRNA-seq studies24.”

    From APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition (2025) · cites this paper as [24]

    The Introduction reports that several human AD snRNA-seq studies find altered cellular pathways, and describes shared disturbances in lipid handling, immune response, and metabolism. It does not establish that these pathways overlap with those altered by a short-term E4-to-E2 transition, or that the finding spans 17 large-scale studies. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Murdock, M. H., & Tsai, L.-H.
Affiliations
Massachusetts Institute of Technology (US)
Corresponding author
Tsai, Li-Huei
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2023-01-02
Volume
26
Issue
2
Pages
181-195
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/s41593-022-01222-2
PMC
PMC10155598
OpenAlex
W4313454730
Cited by
148
References
56
Citations by year
2026: 25 · 2025: 45 · 2024: 51 · 2023: 27
FWCI
4.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
Funders
  • Glenn Foundation for Medical Research
  • Cure Alzheimer's Fund
  • Fondation pour la Recherche Médicale
  • National Institutes of Health (NS051874)
  • National Institute of Neurological Disorders and Stroke (R37NS051874, R01NS051874)
  • National Center for Complementary and Integrative Health (R01AT011460)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, single-cell genomics, amyloid plaques, neurofibrillary tangles, lipid metabolism, immune signaling, metabolic reprogramming, brain cell types, therapeutic interventions, pathogenesis
MeSH terms
Alzheimer Disease, Brain, Humans, Amyloid beta-Peptides, Neurofibrillary Tangles, Genomics, Plaque, Amyloid

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