The Role of Astrocyte-Derived Tau Oligomers in Neurodegeneration Triggered by TBI
Abstract
In AD, studies described a spatial and temporal pattern in the appearance of tau tangles in patient brains that follow neuronal networks and correlates with cognitive decline. While still a contentious topic, there is strong evidence that supports the idea that propagation of pathological tau species occurs between neurons. Microglia and astrocytes have recently been shown to be active participants in the pathological spreading of tau. Nevertheless, the functional significance of propagated glial tau remains to be established. Studies suggest that tau pathology propagation is one of the mechanisms underlying the long term neurodegenerative effects after TBI. The mechanism by how tau propagation in TBI subsequently triggers AD/ADRD pathogenesis is still unknown. Studies have shown how tau appears to be required for A to cause synaptic and cognitive deficits in AD. It was reported that complete ablation of tau prevents deficits in spatial learning and memory after repeated mild frontal impact in WT mice. These results support the idea that reduction of tau could ameliorate the detrimental effects responsible for the association between TBI and AD. Yet no studies have addressed the contribution of exclusively reducing astrocytic tauon reverting AD/ADRD pathogenesis linked to TBI. Hypothesis: Based in these observations in conjunction with our preliminary data, we hypothesize that vascular damage triggered by TBI induces astrocytic-tau aggregation that subsequently promotes tau spreading throughout the brain eliciting synaptotoxicity and neurodegeneration as observed in AD and AD related dementias. Unfortunately, there is no clear understanding of the molecular and cellular mechanisms that underlie the contribution of astrocytic-tau aggregates to neurodegeneration and dementias associated to TBI.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1203248
Entities
People
- Cristian Lasagna-reeves