engleski

Protocol for stereotaxic delivery of tau oligomers and tau fibrils into the rat entorhinal cortex

Sporadic Alzheimer’s disease (AD) is the most common secondary tauopathy characterized by progressive loss of cognitive functions and behavioral impairment. It has been shown that tau pathology progressively spreads in an anatomically stereotypical manner throughout the brain with the first lesions in the locus coeruleus and the entorhinal cortex from where they spread to the hippocampus and high-order neocortical regions. Recent studies on transgenic animal models of AD provide initial evidence that pathogenic protein aggregates could propagate from neuron to neuron, and then self-replicate by templated misfolding of monomeric tau proteins thus igniting further spreading. In this protocol, we describe stereotaxic surgery optimized for delivery of tau oligomers and tau fibrils into the rat entorhinal cortex to assess whether such an intervention will cause a neuron-to-neuron physical spread of tau oligomers and tau aggregates from the site of injection to the entorhinal projecting cortical regions and and will those changes be associated with expected cognitive impairment. We hope that our approach will improve the understanding of mechanisms in spreading of the pathological changes in AD brain and to develop a model that will mimic early events underlying those changes in human disease. The ultimate goal would be to define possible new therapeutic targets and interventions aimed at blocking tau protein oligomerization, aggregation, and spread.

stereotaxic surgery ; tau protein ; entorhinal cortex ; trans-synaptic transfer ; tauopathy ; Alzheimer's disease

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