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Cited by 46Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Neuronal and Glial Distribution of Tau Protein in the Adult Rat and Monkey

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Kanaan, Nicholas M., Grabinski, Tessa·2021·Frontiers in Molecular Neuroscience
DOI 10.3389/fnmol.2021.607303PMC PMC8112591
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Abstract

Tau is a microtubule-associated protein for which the physiological functions remain a topic of vigorous investigation. Additionally, tau is a central player in the pathogenesis of several diseases such as Alzheimer’s disease and several frontotemporal dementias. A critical variable to understanding tau in physiological and disease contexts is its normal localization within cells of the adult CNS. Tau is often described as an axon-specific (or enriched) and neuron-specific protein with little to no expression in glial cells, all of which are untrue. Understanding normal tau distribution also impacts interpretation of experimental results and hypotheses regarding its role in disease. Thus, we set out to help clarify the normal localization of tau in the adult CNS of middle-aged rats and rhesus macaque using the hippocampus as a representative brain structure. The physiological concentration of tau in the rat hippocampus was 6.6 μM and in white matter was 3.6 μM as determined by quantitative sandwich ELISAs. We evaluated the cellular localization of tau using multiple tau-specific antibodies with epitopes to different regions, including Tau1, Tau5, Tau7, R1, and two novel primate-specific antibodies NT9 and NT15. In the rat and monkey, tau was localized within the somatodendritic and axonal compartments, as well as a subset of neuronal nuclei. Semi-quantitative fluorescence intensity measurements revealed that depending on the specific reagent used the somatodendritic tau is relatively equal to, higher than, or lower than axonal tau, highlighting differential labeling of tau with various antibodies despite its distribution throughout the neuron. Tau was strongly expressed in mature oligodendrocytes and displayed little to no expression in oligodendrocyte precursor cells, astrocytes or microglia. Collectively, the data indicate tau is ∼3 – 7 μM under physiological conditions, is not specifically enriched in axons, and is normally found in both neurons and mature oligodendrocytes in the adult CNS. The full landscape of tau distribution is not revealed by all antibodies suggesting availability of the epitopes is different within specific neuronal compartments. These findings set the stage for better understanding normal tau distributions and interpreting data regarding the presence of tau in different compartments or cell types within disease conditions.

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Authors
Kanaan, N. M., & Grabinski, T.
Affiliations
Michigan State University (US)
Corresponding author
Kanaan, Nicholas M.
ORCID
Kanaan, Nicholas M.
Venue
Frontiers in Molecular Neuroscience
Publisher
Frontiers Media SA
Published
2021-04-27
Volume
14
Pages
607303-607303
ISSN
1662-5099 (ISSN-L)
DOI
10.3389/fnmol.2021.607303
PMC
PMC8112591
OpenAlex
W3159335121
Cited by
46
References
90
Citations by year
2026: 9 · 2025: 8 · 2024: 6 · 2023: 12 · 2022: 8 · 2021: 3
FWCI
4.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Michigan State University
  • National Institutes of Health (NS082730)
  • College of Engineering, Michigan State University
  • National Institute on Aging (R01AG044372, P30AG013854, R01AG067762)
  • National Institute of Neurological Disorders and Stroke (R01NS082730)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
tau protein, hippocampus, oligodendrocytes, axonal localization, glial cells, tau antibodies, epitope specificity, white matter, Alzheimer's disease, frontotemporal dementia, rhesus monkeys, rats

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