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

被引：4

作者：

Huhe, Hasi ^{[1
]}

Shapley, Sarah M. ^{[2
]}

Duong, Duc M. ^{[2
]}

Wu, Fang ^{[2
]}

Ha, Seung-Kwon ^{[3
]}

Choi, Sang-Ho ^{[3
]}

Kofler, Julia ^{[4
]}

Mou, Yongshan ^{[3
]}

Guimaraes, Thais Rafael ^{[3
]}

Thathiah, Amantha ^{[3
]}

Watson, Caroline M. ^{[2
]}

Schaeffer, Lauren K. H. ^{[3
]}

Carter, Gregory W. ^{[5
]}

Seyfried, Nicholas T. ^{[2
]}

Silva, Afonso C. ^{[3
]}

Rizzo, Stacey J. Sukoff ^{[1
,3
]}

机构：

[1] Univ Pittsburgh, Aging Inst, Sch Med, 100 Technol Dr, Pittsburgh, PA 15219 USA

[2] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30307 USA

[3] Univ Pittsburgh, Sch Med, Dept Neurobiol, 100 technol Dr, Pittsburgh, PA 15219 USA

[4] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA

[5] Jackson Lab, Bar Harbor, ME USA

来源：

ALZHEIMERS & DEMENTIA | 2025年 / 21卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Alzheimer's disease; biomarkers; marmosets; tau; PAIRED HELICAL FILAMENTS; PROTEIN-TAU; HYPERPHOSPHORYLATED TAU; OLIGOMERS; BRAIN; DEGENERATION; PATHOLOGY; TANGLES; CORTEX;

D O I：

10.1002/alz.14366

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

INTRODUCTION: Marmosets spontaneously develop pathological hallmarks of Alzheimer's disease (AD) including amyloid beta plaques. However, tau expression in the marmoset brain has been understudied. 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 approximate to 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. 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.

引用

页数：16

共 67 条

[1] Hyperphosphorylation induces self-assembly of τ into tangles of paired helical filaments/straight filaments [J].

Alonso, AD ;

Zaidi, T ;

Novak, M ;

Grundke-Iqbal, I ;

Iqbal, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (12) :6923-6928

[2]

[Anonymous], 2011, The Gulf of Mexico at a Glance: A Second Glance, P1, DOI [10.17226/12910, DOI 10.17226/12910]

[3] Studies of aging nonhuman primates illuminate the etiology of early-stage Alzheimer's-like neuropathology: An evolutionary perspective [J].

Arnsten, Amy F. T. ;

Datta, Dibyadeep ;

Preuss, Todd M. .

AMERICAN JOURNAL OF PRIMATOLOGY, 2021, 83 (11)

[4] CSF tau phosphorylation occupancies at T217 and T205 represent improved biomarkers of amyloid and tau pathology in Alzheimer's disease [J].

Barthelemy, Nicolas R. ;

Saef, Benjamin ;

Li, Yan ;

Gordon, Brian A. ;

He, Yingxin ;

Horie, Kanta ;

Stomrud, Erik ;

Salvado, Gemma ;

Janelidze, Shorena ;

Sato, Chihiro ;

Ovod, Vitaliy ;

Henson, Rachel L. ;

Fagan, Anne M. ;

Benzinger, Tammie L. S. ;

Xiong, Chengjie ;

Morris, John C. ;

Hansson, Oskar ;

Bateman, Randall J. ;

Schindler, Suzanne E. .

NATURE AGING, 2023, 3 (04) :391-+

[5] A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer's disease [J].

Barthelemy, Nicolas R. ;

Li, Yan ;

Joseph-Mathurin, Nelly ;

Gordon, Brian A. ;

Hassenstab, Jason ;

Benzinger, Tammie. L. S. ;

Buckles, Virginia ;

Fagan, Anne M. ;

Perrin, Richard J. ;

Goate, Alison M. ;

Morris, John C. ;

Karch, Celeste M. ;

Xiong, Chengjie ;

Allegri, Ricardo ;

Mendez, Patricio Chrem ;

Berman, Sarah B. ;

Ikeuchi, Takeshi ;

Mori, Hiroshi ;

Shimada, Hiroyuki ;

Shoji, Mikio ;

Suzuki, Kazushi ;

Noble, James ;

Farlow, Martin ;

Chhatwal, Jasmeer ;

Graff-Radford, Neill R. ;

Salloway, Stephen ;

Schofield, Peter R. ;

Masters, Colin L. ;

Martins, Ralph N. ;

O'Connor, Antoinette ;

Fox, Nick C. ;

Levin, Johannes ;

Jucker, Mathias ;

Gabelle, Audrey ;

Lehmann, Sylvain ;

Sato, Chihiro ;

Bateman, Randall J. ;

McDade, Eric ;

Allegri, Ricardo ;

Bateman, Randy ;

Bechara, Jacob ;

Benzinger, Tammie ;

Berman, Sarah ;

Bodge, Courtney ;

Brandon, Susan ;

Brooks, William ;

Buck, Jill ;

Buckles, Virginia ;

Chea, Sochenda .

NATURE MEDICINE, 2020, 26 (03) :398-+

[6] Spreading of Tau Pathology in Sporadic Alzheimer's Disease Along Cortico-cortical Top-Down Connections [J].

Braak, Heiko ;

Del Tredici, Kelly .

CEREBRAL CORTEX, 2018, 28 (09) :3372-3384

[7] Interactive Peptide Spectral Annotator: A Versatile Web-based Tool for Proteomic Applications [J].

Brademan, Dain R. ;

Riley, Nicholas M. ;

Kwiecien, Nicholas W. ;

Coon, Joshua J. .

MOLECULAR & CELLULAR PROTEOMICS, 2019, 18 (08) :S193-S201

[8] cAMP-PKA phosphorylation of tau confers risk for degeneration in aging association cortex [J].

Carlyle, Becky C. ;

Nairn, Angus C. ;

Wang, Min ;

Yang, Yang ;

Jin, Lu E. ;

Simen, Arthur A. ;

Ramos, Brian P. ;

Bordner, Kelly A. ;

Craft, George E. ;

Davies, Peter ;

Pletikos, Mihovil ;

Sestan, Nenad ;

Arnsten, Amy F. T. ;

Paspalas, Constantinos D. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (13) :5036-5041

[9] Tau protein is involved in morphological plasticity in hippocampal neurons in response to BDNF [J].

Chen, Qian ;

Zhou, Zhou ;

Zhang, Lei ;

Wang, Yuan ;

Zhang, Yan-wen ;

Zhong, Min ;

Xu, Shang-cheng ;

Chen, Chun-hai ;

Li, Li ;

Yu, Zheng-ping .

NEUROCHEMISTRY INTERNATIONAL, 2012, 60 (03) :233-242

[10] Tau isoforms are differentially expressed across the hippocampus in chronic traumatic encephalopathy and Alzheimer's disease [J].

Cherry, Jonathan D. ;

Esnault, Camille D. ;

Baucom, Zachary H. ;

Tripodis, Yorghos ;

Huber, Bertrand R. ;

Alvarez, Victor E. ;

Stein, Thor D. ;

Dickson, Dennis W. ;

McKee, Ann C. .

ACTA NEUROPATHOLOGICA COMMUNICATIONS, 2021, 9 (01)

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