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

基因亚型 神经科学 疾病 表达式(计算机科学) 磷酸化 心理学 生物 医学 遗传学 内科学 计算机科学 基因 程序设计语言
作者
Hasi Huhe,Sarah Shapley,Duc M. Duong,Fang Wu,Seung‐Kwon Ha,Sangho Choi,Julia Kofler,Yongshan Mou,Thais Rafael Guimarães,Amantha Thathiah,Caroline M. Watson,Lauren K Hayrynen Schaeffer,Gregory W. Carter,Nicholas T. Seyfried,Afonso C. Silva,Stacey J. Sukoff Rizzo
出处
期刊:Alzheimers & Dementia [Wiley]
卷期号:21 (1) 被引量:1
标识
DOI:10.1002/alz.14366
摘要

Marmosets spontaneously develop pathological hallmarks of Alzheimer's disease (AD) including amyloid beta plaques. However, tau expression in the marmoset brain has been understudied. Isoforms of tau were examined by western blot, mass spectrometry, immunofluorescence, and immunohistochemical staining. 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. 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.
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