Cobos Lab

Stanford University

PATHOLOGY

Stanford · United States

NIH-funded
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NIH R01 · 2024

Multidimensional mapping of vulnerable cell types in humanized Alzheimer's disease mouse models

ABSTRACT Alzheimer’s disease (AD) is characterized by progressive neurodegeneration and the aggregation of amyloid-b (Ab) and tau. The selective vulnerability of different brain regions and some cell types to AD pathology has been established. However, much remains unknown regarding the disease-relevant mechanisms underlying this differential response. We have previously used single-cell transcriptomics to perform an unbiased characterization of vulnerable and resistant neuronal subtypes in the human AD brain (19 excitatory and 24 inhibitory subtypes; ~490,000 nuclei, multi-region dataset). This characterization revealed early transcriptional changes in inhibitory interneurons, particularly…

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