Abstract
Tauopathies are a heterogeneous class of neurodegenerative diseases characterized by intracellular inclusions of aggregated tau proteins. Tau aggregates in different tauopathies have distinct structural features and can be found in different cell types. Transgenic animal models overexpressing human tau have been used for over two decades in the research of tau pathology. However, these models poorly recapitulate the heterogeneity of tauopathies found in human brains. Recent findings demonstrate that injection of purified tau aggregates from the brains of human tauopathy patients recapitulates both the structural features and cell-type specificity of the tau pathology of the donor tauopathy. These models may therefore have unique translational value in the study of functional consequences of tau pathology, tau-based diagnostics, and tau targeting therapeutics. This review provides an update of the literature relating to seeding-based tauopathy and their potential applications.
Highlights
Tauopathies are a class of neurodegenerative diseases characterized by intracellular inclusions of aggregated tau proteins
Given the recent focus on the mechanisms of tau propagation, there has been an increasing interest in animal models with localized tau pathology. These models can be roughly classified into four categories: localized Tg tau models with expression of mutated tau restricted to the entorhinal cortex (EC), adeno-associated virus (AAV)-based models with inducible tau expression, seeding-based models injected with recombinant tau fibrils, and seeding-based models injected with human brain-derived tau fibrils
Despite the successful seeding and spreading of pathological tau following injection of brain extracts derived from human patients, they reported a failure to recapitulate some of the hallmark features of tauopathies, such as globular oligodendroglial and astroglial inclusions in Globular glial tauopathy (GGT) or thorn-shaped astrocytes upon aging-related tau astrogliopathy (ARTAG)-tau inoculation
Summary
Tauopathies are a class of neurodegenerative diseases characterized by intracellular inclusions of aggregated tau proteins. Tau pathology along Braak stages in AD appears to progress along neuroanatomically connected brain regions [7,8,9] This has been suggested to occur by means of spreading of tau aggregates to synaptically connected neurons and subsequent seeded aggregation of physiological tau proteins in previously unaffected cells [10,11,12,13]. Several aspects of tau pathology in tauopathy patients have been successfully modelled in transgenic mice overexpressing human tau, including tau-associated processes such as neuroinflammation, synapse loss, neurodegeneration, and cognitive impairment [14,15]. Efforts to develop animal models with improved translational value have led to the emergence of seeding-based animal models injected with tau aggregates derived from patients with different tauopathies [18] These models represent a significant advance in several aspects. The use of more translationally relevant models to determine the exact mechanisms underlying PTMs and their implications on a functional level may be required
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