Document Type
Article
Publication Date
1-1-2025
Original Citation
Huhe H,
Shapley S,
Duong D,
Wu F,
Ha S,
Choi S,
Kofler J,
Mou Y,
Guimaraes T,
Thathiah A,
Watson C,
Schaeffer L,
Carter GW,
Seyfried N,
Silva A,
Sukoff Rizzo S.
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. Alzheimers Dement. 2025;21(1):e14366.
Keywords
JMG, Callithrix, Animals, Phosphorylation, tau Proteins, Protein Isoforms, Disease Models, Animal, Brain, Alzheimer Disease, Humans, Male, Female
JAX Source
Alzheimers Dement. 2025;21(1):e14366.
ISSN
1552-5279
PMID
39559898
DOI
https://doi.org/10.1002/alz.14366
Grant
National Institutes of Health, Grant/Award Number: U19AG074866; National Institute on Aging, Grant/Award Number: R24AG073190
Abstract
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.