Marmosets as model systems for the study of Alzheimer's disease and related dementias: Substantiation of physiological tau 3R and 4R isoform expression and phosphorylation

狨猴作为研究阿尔茨海默病和相关痴呆症的模型系统:生理性 tau 3R 和 4R 同工酶表达和磷酸化的证实

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作者:Hasi Huhe, Sarah M Shapley, Duc M Duong, Fang Wu, Seung-Kwon Ha, Sang-Ho Choi, Julia Kofler, Yongshan Mou, Thais Rafael Guimaraes, Amantha Thathiah, Caroline M Watson, Lauren K H Schaeffer, Gregory W Carter, Nicholas T Seyfried, Afonso C Silva, Stacey J Sukoff Rizzo

Discussion

Our results confirm both 3R and 4R tau isoform expression and phosphorylation residues in the marmoset brain, and emphasize the significance of marmosets with natural expression of AD-related hallmarks as important translational models for AD. Highlights We report comprehensive characterization of tau isoform expression in marmoset brains across the lifespan. 3R and 4R tau isoforms are expressed in marmoset brains at both the transcript and protein levels across ages. These data emphasize the significance of marmosets with natural expression of primate-specific traits that are important for the study of Alzheimer's disease.

Methods

Isoforms of tau were examined by western blot, mass spectrometry, immunofluorescence, and immunohistochemical staining.

Results

3R and 4R tau isoforms are expressed in marmoset brains at both the transcript and protein levels across ages. Mass spectrometry analysis revealed that tau peptides in marmoset corresponded to the 3R and 4R peptides in human brain, with 3R predominating at birth and an ≈40%:60% 3R:4R ratios in adolescents and adults; tau was distributed widely in neurons, with localization in the soma and synaptic regions. Phosphorylation residues were observed on Threonine (Thr) Thr181, Thr217, Thr231, Serine (Ser) Ser202/Thr205, and Ser396/Ser404.

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