Expansion of highly interferon-responsive T cells in early-onset Alzheimer's disease.

Introduction: 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).

Methods: 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.

Results: We analyzed PBMCs from 16 individuals by scRNA-seq and discovered increased interferon signaling-associated gene (ISAG) expression and striking expansion of antiviral-like ISAG T cells in EOAD.

Expansion of highly interferon-responsive T cells in early-onset Alzheimer's disease.

Introduction: 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).

Methods: We examined single-cell RNA-sequencing (scRNA-seq) data from peripheral blood mononuclear cells (PBMCs) and droplet digital (dd)PCR data from CD4 T cells from participants with EOAD and clinically normal controls.

Results: We analyzed ~182,000 PBMCs by scRNA-seq and discovered increased interferon signaling-associated gene (ISAG) expression and striking expansion of antiviral-like ISAG T cells in EOAD.

Single-cell RNA-seq reveals alterations in peripheral CX3CR1 and nonclassical monocytes in familial tauopathy.

Background: Emerging evidence from mouse models is beginning to elucidate the brain's immune response to tau pathology, but little is known about the nature of this response in humans. In addition, it remains unclear to what extent tau pathology and the local inflammatory response within the brain influence the broader immune system.

Methods: To address these questions, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from carriers of pathogenic variants in MAPT, the gene encoding tau (n = 8), and healthy non-carrier controls (n = 8).

Dissecting the clinical heterogeneity of early-onset Alzheimer's disease.

Early-onset Alzheimer's disease (EOAD) is a rare but particularly devastating form of AD. Though notable for its high degree of clinical heterogeneity, EOAD is defined by the same neuropathological hallmarks underlying the more common, late-onset form of AD. In this review, we describe the various clinical syndromes associated with EOAD, including the typical amnestic phenotype as well as atypical variants affecting visuospatial, language, executive, behavioral, and motor functions.