Open AccessNasal Extracts from Patients with Alzheimer’s Disease Induce Tau Aggregates in a Cellular Model of Tau Propagation
Author(s) -
Aslina Pahrudin Arrozi,
Daijiro Yanagisawa,
Tomoko Kato,
Hiroyasu Akatsu,
Yoshio Hashizume,
Daita Kaneda,
Ikuo Tooyama
Publication year - 2021
Publication title -
journal of alzheimer's disease reports
Language(s) - English
Resource type - Journals
ISSN - 2542-4823
DOI - 10.3233/adr-210298
Subject(s) - tau protein , tau pathology , mucous membrane of nose , olfactory mucosa , hek 293 cells , tauopathy , nasal cavity , green fluorescent protein , brain tissue , microbiology and biotechnology , chemistry , cell culture , biology , pathology , alzheimer's disease , olfactory system , immunology , medicine , neuroscience , disease , biochemistry , anatomy , gene , neurodegeneration , genetics
Background: Emerging evidence indicates that the misfolded tau protein can propagate aggregates between cells in a prion-like manner. This prion activity has been typically studied in brain extracts of patients with Alzheimer’s disease (AD), but not in the olfactory region that can be a potential biomarker in AD. Objective: To investigate the prion seeding activity of tau in nasal mucosa tissues using a cell culture model of tau propagation. Methods: Brain and nasal mucosa homogenates were added to HEK293T cells expressing three repeat or four-repeat domains of tau with the L266V, V337M (3RD*VM) and P301L and V377M mutations (4RD*LM) fused to the enhanced green fluorescence protein (EGFP) respectively. We also measured the level of phosphorylated tau (p-tau), total tau (t-tau), and p-tau/t-tau ratio and performed correlation analysis between tau prion activity and the level of tau. Results: We found that brain and nasal tissue homogenates from patients with AD significantly induced tau aggregation in HEK293T cells either expressing tau 3RD*VM-EGFP or 4RD*LM-EGFP compared with control brain and nasal tissue homogenates. The levels of p-tau and p-tau/t-tau ratio were significantly increased in the brain of patients with AD; however, no significant difference was found in nasal tissue compared with their respective control tissue homogenates. Conclusion: These results suggest that the nasal tissues contain tau seeds, similar to the brain, albeit without changes in the levels of p-tau and t-tau. Therefore, a cellular bioassay using nasal tissues would have great potential as an AD biomarker because of the usefulness of nasal tissue biopsy.