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At the time the article was created Frank Gaillard had no recorded disclosures.View Frank Gaillard's current disclosures
At the time the article was last revised Henry Knipe had the following disclosures:
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Tauopathies are a heterogeneous group of neurodegenerative diseases characterized by abnormal metabolism of misfolded τ (tau) proteins leading to intracellular accumulation and formation of neurofibrillary tangles (NFT). These neurofibrillary tangles are deposited in the cytosol of neurons and glial cells.
Examples of tauopathies include 3:
Alzheimer disease (considered a secondary tauopathy)
It should be noted that some texts 2 define tauopathies as a disease characterized by mutations in the τ protein gene itself. If such a strict definition is used, even though the histopathological hallmark of Alzheimer disease is the presence of numerous neurofibrillary tangles (which are also formed by τ proteins), it still would not be strictly a tauopathy, as no defect in the tau protein gene has been identified. Thus, it is referred to as a secondary tauopathy as β-amyloid accumulation is considered the primary pathology 5.
Tauopathies are the result of aggregation and precipitation of misfolded τ proteins that normally stabilize neural microtubules. These aggregates form neurofibrillary tangles that in turn lead to neuronal toxicity and degeneration.
Misfolded τ proteins from two distinct aggregates: three repeat (3R) and four repeat (4R) which variably present in different diseases 5.
More recently the discovery of the glymphatic pathway and the importance of this in the normal physiological clearance of extracellular solutes including beta-amyloid, suggests that there is also the possibility of reduced clearance, in addition to abnormal metabolism, as the underpinning of some tauopathies including chronic traumatic encephalopathy 4.
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- 3. Williams DR. Tauopathies: classification and clinical update on neurodegenerative diseases associated with microtubule-associated protein tau. Intern Med J. 2006;36 (10): 652-60. doi:10.1111/j.1445-5994.2006.01153.x - Pubmed citation
- 4. Koliatsos VE and Xu L. The Problem of Neurodegeneration in Cumulative Sports Concussions: Emphasis on Neurofibrillary Tangle Formation. Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. Read it free
- 5. Kunal P. Patel, David T. Wymer, Vinay K. Bhatia, Ranjan Duara, Chetan D. Rajadhyaksha. Multimodality Imaging of Dementia: Clinical Importance and Role of Integrated Anatomic and Molecular Imaging. (2020) RadioGraphics. 40 (1): 200-222. doi:10.1148/rg.2020190070 - Pubmed