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P4‐087: TAU Oligomers and Inflammation: Their Association and Implications for Spreading and Therapy
Author(s) -
Nilson Ashley N.,
English Kelsey,
Gerson Julia E.,
Farmer Kathleen,
Sengupta Urmi,
Castillo-Carranza Diana L.,
Masel Todd,
Kayed Rakiz
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.2176
Subject(s) - microglia , inflammation , neurodegeneration , tauopathy , tau protein , frontotemporal dementia , disease , neuroscience , chemistry , dementia , alzheimer's disease , microbiology and biotechnology , biology , immunology , medicine , pathology
Background:Inflammation has beenwell-established to play an important role in age-related neurodegenerative diseases including tauopathies such as Alzheimer’s disease (AD) and Frontotemporal Lobar dementia (FTLD). Inflammation and cell death appear in disease prior to the formation of larger aggregates. While amyloid-b has been wellstudied in relation to inflammation, the contribution of tau protein has not yet been thoroughly investigated. Although tau in healthy brain cells exists as an unfolded monomer with many important functions, in disease states it aggregates to form large fibrillar structures known as neurofibrillary tangles. However, evidence suggests that smaller soluble aggregates—oligomers—that are formed prior to tangles are in fact themost toxic species. In addition to being locally toxic to neurons, tau oligomers can spread to both adjacent and synaptically connected brain regions. Here we examined the relationship of tau oligomers and inflammationwhich are hallmarks of early disease states.Methods: We evaluated human brain samples from bothAD and FTLD cases using immunofluorescence and biochemical analysis for a potential interaction between tau oligomers and inflammation. Results: We showed that in human and mouse tissues, in addition to the elevated of inflammation markers, tau oligomers co-localize with microglia and activated astrocytes appear. Additionally, the inflammatory factor, HMGB1, which has been shown to be elevated in neurodegeneration, was observed to co-localize with tau oligomers. Conclusions:These results suggest a potential toxic relationship between tau oligomers and inflammation in neurodegenerative disease. Therefore, the ability of tau oligomers to spread may initiate a feed-forward cycle in which tau oligomers induce inflammation leading to neuronal damage and thus more inflammation. These conditions may also create an environment more favorable to tau aggregation. Further mechanistic study to better understand the relationshipbetween tauand inflammation iswarranted andmay have critical implications for the progression and treatment of tauopathies.