INTRODUCTIONMarmosets spontaneously develop pathological hallmarks of Alzheimer's disease (AD) including amyloid beta plaques. However, tau expression in the marmoset brain has been understudied.METHODSIsoforms of tau were examined by western blot, mass spectrometry, immunofluorescence, and immunohistochemical staining.RESULTS3R 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.DISCUSSIONOur 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.

中文翻译：

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狨猴作为阿尔茨海默病和相关痴呆症研究的模型系统：生理性 tau 3R 和 4R 亚型表达和磷酸化的证实


引言 分子自发出现阿尔茨海默病 （AD） 的病理标志，包括 β 淀粉样蛋白斑块。然而，狨猴大脑中的 tau 表达尚未得到充分研究。方法通过 western blot、质谱、免疫荧光和免疫组化染色检测 tau 的体型。RESULTS3R 和 4R tau 亚型在狨猴大脑中在不同年龄的转录和蛋白质水平上均表达。质谱分析显示，狨猴中的 tau 肽对应于人脑中的 3R 和 4R 肽，出生时 3R 占主导地位，青少年和成人的 3R：4R 比值为 ≈40%：60%;tau 广泛分布在神经元中，定位于 soma 和 synaptic 区域。在苏氨酸 （Thr） Thr181、Thr217、Thr231、丝氨酸 （Ser） Ser202/Thr205 和 Ser396/Ser404 上观察到磷酸化残基。亮点 我们报告了狨猴大脑中 tau 亚型在整个生命周期中表达的全面特征。3R 和 4R tau 亚型在狨猴大脑中在不同年龄的转录水平和蛋白质水平上均表达。这些数据强调了狨猴自然表达灵长类动物特异性特征的重要性，这些特征对阿尔茨海默病的研究很重要。