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.

Autor: Huhe H; Aging Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Shapley SM; Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA., Duong DM; Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA., Wu F; Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA., Ha SK; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Choi SH; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Kofler J; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Mou Y; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Guimaraes TR; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Thathiah A; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Watson CM; Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA., Schaeffer LKH; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Carter GW; The Jackson Laboratory, Bar Harbor, Maine, USA., Seyfried NT; Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA., Silva AC; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Sukoff Rizzo SJ; Aging Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2024 Nov 19. Date of Electronic Publication: 2024 Nov 19.
DOI: 10.1002/alz.14366
Abstrakt: 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 ≈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. 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.
(© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE
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