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Cellular and pathological heterogeneity of primary tauopathies
- Source :
- Molecular Neurodegeneration, Molecular Neurodegeneration, Vol 16, Iss 1, Pp 1-20 (2021)
- Publication Year :
- 2020
-
Abstract
- Microtubule-associated protein tau is abnormally aggregated in neuronal and glial cells in a range of neurodegenerative diseases that are collectively referred to as tauopathies. Multiple studies have suggested that pathological tau species may act as a seed that promotes aggregation of endogenous tau in naïve cells and contributes to propagation of tau pathology. While they share pathological tau aggregation as a common feature, tauopathies are distinct from one another with respect to predominant tau isoforms that accumulate and the selective vulnerability of brain regions and cell types that have tau inclusions. For instance, primary tauopathies present with glial tau pathology, while it is mostly neuronal in Alzheimer’s disease (AD). Also, morphologies of tau inclusions can greatly vary even within the same cell type, suggesting distinct mechanisms or distinct tau conformers in each tauopathy. Neuropathological heterogeneity across tauopathies challenges our understanding of pathophysiology behind tau seeding and aggregation, as well as our efforts to develop effective therapeutic strategies for AD and other tauopathies. In this review, we describe diverse neuropathological features of tau inclusions in neurodegenerative tauopathies and discuss what has been learned from experimental studies with mouse models, advanced transcriptomics, and cryo-electron microscopy (cryo-EM) on the biology underlying cell type-specific tau pathology.
- Subjects :
- Cell
Review
Transcriptome
Mice
Brain Injuries, Traumatic
MAPT
Protein Isoforms
Cryo-EM
Neurons
biology
Microglia
Neurodegenerative Diseases
Recombinant Proteins
Tau isoforms
Animal models
Oligodendroglia
Tauopathy
medicine.anatomical_structure
Tauopathies
Frontotemporal Dementia
Disease Susceptibility
Neuroglia
Cell type
Tau protein
Mice, Transgenic
tau Proteins
Protein Aggregation, Pathological
Cellular and Molecular Neuroscience
mental disorders
medicine
Animals
Humans
RC346-429
Transcriptomics
Molecular Biology
Pathological
Cryoelectron Microscopy
RC952-954.6
medicine.disease
Disease Models, Animal
Geriatrics
Astrocytes
Chronic Disease
Mutation
biology.protein
Gene-Environment Interaction
Neurology. Diseases of the nervous system
Neurology (clinical)
Tau
Neuroscience
Subjects
Details
- ISSN :
- 17501326
- Volume :
- 16
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular neurodegeneration
- Accession number :
- edsair.doi.dedup.....8cf6d97d5370db2a0ff0fc0fec2645fe