In vitro cell modeling of tau protein spread in Alzheimer's disease pathology

Identification: Chin, Marcus


Description

In vitro cell modeling of tau protein spread in Alzheimer's disease pathology
 
Marcus Chin1, Xu Chen1, Sue-Ann Mok2, Jason Gestwicki2*, and Li Gan1*
1Gladstone Institute of Neurological Disease; 2Institute of Neurodegenerative Disease, University of California, San Francisco
*Corresponding Author
 
Alzheimer's disease (AD) and other tauopathies are characterized by a classical pathological hallmark called neurofibrillary tangles (NFT), which are composed of aggregates of hyperphosphorylated tau protein.  Multiple clinicopathological studies have supported the correlation between the amount and distribution of NFTs with the severity and duration of AD.  As a result, it seems that tau pathology follows a distinct neuroanatomical pathway that can act as a route for spread throughout the brain.  Mutations in tau are also implicated to cause neurodegeneration, although the exact pathological role of such mutants is currently unknown.  My project utilized a previously described in vitro neuron model to recapitulate tau propagation after introduction of exogenous tau protein fibrils and monomers.  After seven days of treatment, neurons were imaged for MC1 positivity, a measure for aggregated tau.  The P301L tau mutant induced significantly more MC1 positive neurons than wildtype, which corroborates with previous studies supporting P301L tau pathogenicity in the brain.   
 

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