Tauopathies: new perspectives and challenges

Zhang, Yi; Wu, Kai-Min; Yang, Liu; Dong, Qiang; Yu, Jin-Tai

doi:10.1186/s13024-022-00533-z

Cited by 329Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchAmyotrophic Lateral Sclerosis Research

Tauopathies: new perspectives and challenges

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Zhang, Yi, Wu, Kai-Min, Yang, Liu, Dong, Qiang, Yu, Jin-Tai·2022·Molecular Neurodegeneration

DOI 10.1186/s13024-022-00533-zPMC PMC8991707

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Abstract

Background: Tauopathies are a class of neurodegenerative disorders characterized by neuronal and/or glial tau-positive inclusions. Main body: Clinically, tauopathies can present with a range of phenotypes that include cognitive/behavioral-disorders, movement disorders, language disorders and non-specific amnestic symptoms in advanced age. Pathologically, tauopathies can be classified based on the predominant tau isoforms that are present in the inclusion bodies (i.e., 3R, 4R or equal 3R:4R ratio). Imaging, cerebrospinal fluid (CSF) and blood-based tau biomarkers have the potential to be used as a routine diagnostic strategy and in the evaluation of patients with tauopathies. As tauopathies are strongly linked neuropathologically and genetically to tau protein abnormalities, there is a growing interest in pursuing of tau-directed therapeutics for the disorders. Here we synthesize emerging lessons on tauopathies from clinical, pathological, genetic, and experimental studies toward a unified concept of these disorders that may accelerate the therapeutics. Conclusions: Since tauopathies are still untreatable diseases, efforts have been made to depict clinical and pathological characteristics, identify biomarkers, elucidate underlying pathogenesis to achieve early diagnosis and develop disease-modifying therapies.

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Both 3R- and 4R-tau isoforms were detected with no noticeable difference in the 3R to 4R ratio between LOAD and HC 3D-CNs.
“Both 3R- and 4R-tau isoforms were detected with no noticeable difference in the 3R to 4R ratio between LOAD and HC 3D-CNs, consistent with the concept that AD is a mixed 3R/4R tauopathy (65, 66) (Fig. 3D).”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [66]

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Ubiquitin Specific Protease 13 Regulates Tau Accumulation and Clearance in Models of Alzheimer’s Disease1
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Regional [18F]flortaucipir PET is more closely associated with disease severity than CSF p-tau in Alzheimer’s disease
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Anti-tau scFvs Targeted to the Cytoplasm or Secretory Pathway Variably Modify Pathology and Neurodegenerative Phenotypes
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Longitudinal Association of Total Tau Concentrations and Physical Activity With Cognitive Decline in a Population Sample
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The molecular tweezer CLR01 improves behavioral deficits and reduces tau pathology in P301S-tau transgenic mice
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ATN incorporating cerebrospinal fluid neurofilament light chain detects frontotemporal lobar degeneration
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Active immunization with tau epitope in a mouse model of tauopathy induced strong antibody response together with improvement in short memory and pSer396-tau pathology
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Visualization of soluble tau oligomers in TauP301L-BiFC transgenic mice demonstrates the progression of tauopathy
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Neuroprotective Approach of Anti-Cancer Microtubule Stabilizers Against Tauopathy Associated Dementia: Current Status of Clinical and Preclinical Findings
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Factors associated with development and distribution of granular/fuzzy astrocytes in neurodegenerative diseases
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Argyrophilic grain disease in individuals younger than 75 years: clinical variability in an under‐recognized limbic tauopathy
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Chronic Sodium Selenate Treatment Restores Deficits in Cognition and Synaptic Plasticity in a Murine Model of Tauopathy
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[92]Boxer AL Yu JT Golbe LI Litvan I Lang AE Höglinger GU Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches Lancet Neurol 2017 10.1016/s1474-4422(17)30157-6 28653647 PMC5802400 · DOI · Paper page

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“Both 3R-and 4R-tau isoforms were detected with no noticeable difference in the 3R to 4R ratio between LOAD and HC 3D-CNs, consistent with the concept that AD is a mixed 3R/4R tauopathy (65, 66) (Fig.”
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Authors: Zhang, Y., Wu, K.-M., Yang, L., Dong, Q., & Yu, J.-T.
Affiliations: Shanghai Medical College of Fudan University (CN)
Corresponding author: Yu, Jin-Tai
ORCID: Zhang, Yi
Dong, Qiang
Yu, Jin-Tai
Venue: Molecular Neurodegeneration
Publisher: Springer Science and Business Media LLC
Published: 2022-04-07
Volume: 17
Issue: 1
Pages: 28-28
ISSN: 1750-1326 (ISSN-L)
DOI: 10.1186/s13024-022-00533-z
PMC: PMC8991707
OpenAlex: W4223629343
Cited by: 323
References: 228
Citations by year: 2026: 69 · 2025: 83 · 2024: 97 · 2023: 60 · 2022: 14
FWCI: 8.91
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Molecular Neurodegeneration (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: National Natural Science Foundation of China (91849126)
Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords: tauopathy, tau protein, neurodegenerative diseases, tau isoforms, tau biomarkers, cerebrospinal fluid biomarkers, blood-based biomarkers, neuroimaging, disease-modifying therapy, early diagnosis
MeSH terms: Inclusion Bodies, Humans, Neurons, tau Proteins, Neurodegenerative Diseases, Protein Isoforms, Tauopathies

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