Altered immune signatures are emerging as a central theme in neurodegenerative disease, yet little is known about immune responses in early-onset Alzheimer’s disease (EOAD).
We examined single-cell RNA-sequencing (scRNA-seq) data from peripheral blood mononuclear cells (PBMCs) and droplet digital polymerase chain reaction (ddPCR) data from CD4 T cells from participants with EOAD and clinically normal controls.
We analyzed PBMCs from 16 individuals by scRNA-seq and discovered increased interferon signaling-associated gene (ISAG) expression and striking expansion of antiviral-like ISAGhi T cells in EOAD. Isolating CD4 T cells from 19 individuals, including four cases analyzed by scRNA-seq, we confirmed increased expression of ISAGhi marker genes. Publicly available cerebrospinal fluid leukocyte scRNA-seq data from late-onset mild cognitive impairment and AD also revealed increased expression of interferon-response genes.
Antiviral-like ISAGhi T cells are expanded in EOAD. Additional research into these cells and the role of heightened peripheral IFN signaling in neurodegeneration is warranted.

Interferon-responsive T cells expanded in early-onset Alzheimer’s disease (AD).
Increased interferon-associated gene expression present in early- and late-onset AD.
Peripheral immune changes in T and NK cells driven by females with early-onset AD.

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This post is Copyright: Daniel W. Sirkis,
Caroline Warly Solsberg,
Taylor P. Johnson,
Luke W. Bonham,
Alexis P. Oddi,
Ethan G. Geier,
Bruce L. Miller,
Gil D. Rabinovici,
Jennifer S. Yokoyama | June 3, 2024

Wiley: Alzheimer’s & Dementia: Table of Contents