Dataset Information

A1-Reactive Astrocytes and a loss of TREM2 are associated to an early state of pathology in a mouse model of Cerebral Amyloid Angiopathy

ABSTRACT: In this study, we dissect in detail the glial and immune responses associated to early stages of CAA. To do so, RNAseq gene expression analysis were performed in a mouse model for Familial Danish Dementia (FDD), a neurodegenerative disease characterized by the accumulation of Danish amyloid (ADan) in the vasculature. Findings observed in this CAA mouse model were complemented with primary culture assays.

ORGANISM(S): Mus musculus

PROVIDER: GSE150394 | GEO | 2020/07/22

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:BackgroundCerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. The mechanisms underlying the contribution of CAA to neurodegeneration are not currently understood. Although CAA is highly associated with the accumulation of amyloid beta (Aβ), other amyloids are known to associate with the vasculature. Alzheimer's disease (AD) is characterized by parenchymal Aβ deposition, intracellular accumulation of tau, and significant neuroinflammation. CAA increases with age and is present in 85-95% of individuals with AD. A substantial amount of research has focused on understanding the connection between parenchymal amyloid and glial activation and neuroinflammation, while associations between vascular amyloid pathology and glial reactivity remain understudied.MethodsHere, we dissect the glial and immune responses associated with early-stage CAA with histological, biochemical, and gene expression analyses in a mouse model of familial Danish dementia (FDD), a neurodegenerative disease characterized by the vascular accumulation of Danish amyloid (ADan). Findings observed in this CAA mouse model were complemented with primary culture assays.ResultsWe demonstrate that early-stage CAA is associated with dysregulation in immune response networks and lipid processing, severe astrogliosis with an A1 astrocytic phenotype, and decreased levels of TREM2 with no reactive microgliosis. Our results also indicate how cholesterol accumulation and ApoE are associated with vascular amyloid deposits at the early stages of pathology. We also demonstrate A1 astrocytic mediation of TREM2 and microglia homeostasis.ConclusionThe initial glial response associated with early-stage CAA is characterized by the upregulation of A1 astrocytes without significant microglial reactivity. Gene expression analysis revealed that several AD risk factors involved in immune response and lipid processing may also play a preponderant role in CAA. This study contributes to the increasing evidence that brain cholesterol metabolism, ApoE, and TREM2 signaling are major players in the pathogenesis of AD-related dementias, including CAA. Understanding the basis for possible differential effects of glial response, ApoE, and TREM2 signaling on parenchymal plaques versus vascular amyloid deposits provides important insight for developing future therapeutic interventions.

Dataset Information

A1-Reactive Astrocytes and a loss of TREM2 are associated to an early state of pathology in a mouse model of Cerebral Amyloid Angiopathy

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets