Medicine:Tauopathy

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Tauopathy
Taupathy.svg
Diagram of a normal microtubule and one affected by tauopathy

Tauopathy belongs to a class of neurodegenerative diseases involving the aggregation of tau protein into neurofibrillary or gliofibrillary tangles in the human brain. Tangles are formed by hyperphosphorylation of the microtubule protein known as tau, causing the protein to dissociate from microtubules and form insoluble aggregates.[1] (These aggregations are also called paired helical filaments.) The mechanism of tangle formation is not well understood, and whether tangles are a primary cause of Alzheimer's disease or play a peripheral role is unknown.

Detection and imaging

Post-mortem
Tau tangles are seen microscopically in stained brain samples.[2]
Pre-mortem
In living patients tau tangle locations can be imaged with a PET scan using a suitable radio-emissive agent.[3]

Alzheimer's disease

Abnormal accumulation of tau protein in neuronal cell bodies (arrow) and neuronal extensions (arrowhead) in the neocortex of a patient who died with Alzheimer's disease. The bar = 25 microns (0.025 millimeters).

Neurofibrillary tangles were first described by Alois Alzheimer in one of his patients with Alzheimer's disease (AD). The tangles are considered a secondary tauopathy. AD is also classified as an amyloidosis because of the presence of senile plaques.[4]

When tau becomes hyperphosphorylated, the protein dissociates from the microtubules in axons.[5] Then, tau becomes misfolded and the protein begins to aggregate, which eventually forms the neurofibrillary tangles (NFT) seen in Alzheimer's patients.[1] Microtubules also destabilize when tau is dissociated. The combination of the neurofibrillary tangles and destabilized microtubules result in disruption of processes such as axonal transport and neural communication.[6]

The degree of NFT involvement in AD is defined by Braak stages. Braak stages I and II are used when NFT involvement is confined mainly to the transentorhinal region of the brain, stages III and IV when there is also involvement of limbic regions such as the hippocampus, and V and VI when there's extensive neocortical involvement. This should not be confused with the degree of senile plaque involvement, which progresses differently.[7]

Other diseases

In both Pick's disease and corticobasal degeneration, tau proteins are deposited as inclusion bodies within swollen or "ballooned" neurons.

Argyrophilic grain disease (AGD), another type of dementia,[20][21][22] is marked by an abundance of argyrophilic grains and coiled bodies upon microscopic examination of brain tissue.[23] Some consider it to be a type of Alzheimer's disease.[23] It may co-exist with other tauopathies such as progressive supranuclear palsy and corticobasal degeneration,[4] and also Pick's disease.[24]

Tauopathies are often overlapped with synucleinopathies, possibly due to interaction between the synuclein and tau proteins.[25]

The non-Alzheimer's tauopathies are sometimes grouped together as "Pick's complex" due to their association with frontotemporal dementia, or frontotemporal lobar degeneration.[26]

Research

It is found that activation of cannabinoid receptor type 1 (CB1) mediate inhibition of astroglial-derived nitric oxide (NO), that could be used as a new potential target to blunt tau protein hyperphosphorylation and the consequent related tauopathy in Alzheimer disease (AD).[27]

See also

References

  1. ↑ 1.0 1.1 "Propagation of Tau aggregates". Molecular Brain 10 (1): 18. May 2017. doi:10.1186/s13041-017-0298-7. PMID 28558799. 
  2. ↑ "Phosphorylated tau sites that are elevated in Alzheimer's disease fluid biomarkers are visualized in early neurofibrillary tangle maturity levels in the post mortem brain". Alzheimer's & Dementia. May 2022. 
  3. ↑ Alzheimer 'tau' protein far surpasses amyloid in predicting toll on brain tissue
  4. ↑ 4.0 4.1 4.2 "Neuropathology of non-Alzheimer degenerative disorders". International Journal of Clinical and Experimental Pathology 3 (1): 1–23. August 2009. PMID 19918325. 
  5. ↑ "Abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration". Journal of Alzheimer's Disease 33 (Suppl 1): S123-39. 2013. doi:10.3233/JAD-2012-129031. PMID 22710920. 
  6. ↑ "Tau in physiology and pathology". Nature Reviews. Neuroscience 17 (1): 5–21. January 2016. doi:10.1038/nrn.2015.1. PMID 26631930. 
  7. ↑ "Neuropathological stageing of Alzheimer-related changes". Acta Neuropathologica 82 (4): 239–59. 1991. doi:10.1007/BF00308809. PMID 1759558. 
  8. ↑ "The MAPT H1 haplotype is associated with tangle-predominant dementia". Acta Neuropathologica 124 (5): 693–704. November 2012. doi:10.1007/s00401-012-1017-1. PMID 22802095. 
  9. ↑ "Neurofibrillary tangle-predominant dementia: comparison with classical Alzheimer disease". Acta Neuropathologica 113 (2): 107–17. February 2007. doi:10.1007/s00401-006-0156-7. PMID 17089134. 
  10. ↑ "The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy". Acta Neuropathologica 131 (1): 75–86. January 2016. doi:10.1007/s00401-015-1515-z. PMID 26667418. PMC 4698281. http://eprints.gla.ac.uk/115891/1/115891.pdf. 
  11. ↑ "Immunocytochemistry of neurofibrillary tangles in dementia pugilistica and Alzheimer's disease: evidence for common genesis". Lancet 2 (8626–8627): 1456–8. 1988. doi:10.1016/S0140-6736(88)90934-8. PMID 2904573. 
  12. ↑ "Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges". The Lancet. Neurology 8 (3): 270–9. March 2009. doi:10.1016/S1474-4422(09)70042-0. PMID 19233037. 
  13. ↑ "Deciphering the genetic basis of Alzheimer's disease". Annual Review of Genomics and Human Genetics 3: 67–99. 2002. doi:10.1146/annurev.genom.3.022502.103022. PMID 12142353. 
  14. ↑ "Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau". Science 370 (6519): eaay8826. 2020. doi:10.1126/science.aay8826. PMID 33004675. 
  15. ↑ "Amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam: quantitative neuropathology, immunohistochemical analysis of neuronal vulnerability, and comparison with related neurodegenerative disorders". Acta Neuropathologica 88 (5): 397–404. 1994. doi:10.1007/BF00389490. PMID 7847067. 
  16. ↑ "Tau-associated neuropathology in ganglion cell tumours increases with patient age but appears unrelated to ApoE genotype". Neuropathology and Applied Neurobiology 27 (3): 197–205. June 2001. doi:10.1046/j.1365-2990.2001.00311.x. PMID 11489139. 
  17. ↑ "Meningio-angiomatosis: a report of six cases with special reference to the occurrence of neurofibrillary tangles". Journal of Neuropathology and Experimental Neurology 45 (4): 426–46. July 1986. doi:10.1097/00005072-198607000-00005. PMID 3088216. 
  18. ↑ "Neurofibrillary changes in the cerebral cortex of a patient with subacute sclerosing panencephalitis (SSPE)". Acta Neuropathologica 48 (2): 157–60. November 1979. doi:10.1007/BF00691159. PMID 506699. 
  19. ↑ "Alzheimer neurofibrillary tangles in diseases other than senile and presenile dementia". Annals of Neurology 5 (3): 288–94. March 1979. doi:10.1002/ana.410050311. PMID 156000. 
  20. ↑ "Argyrophilic grain disease". Brain 131 (Pt 6): 1416–32. June 2008. doi:10.1093/brain/awm305. PMID 18234698. 
  21. ↑ "Argyrophilic grains: a distinct disease or an additive pathology?". Neurobiology of Aging 29 (4): 566–73. April 2008. doi:10.1016/j.neurobiolaging.2006.10.032. PMID 17188783. 
  22. ↑ "[Argyrophilic grain disease: synergistic component of dementia?]" (in French). Revue Neurologique 166 (4): 428–32. April 2010. doi:10.1016/j.neurol.2009.10.012. PMID 19963233. 
  23. ↑ 23.0 23.1 "[Argyrophilic grain disease: differentiation from Alzheimer disease]". Der Pathologe 20 (3): 159–68. May 1999. doi:10.1007/s002920050339. PMID 10412175. 
  24. ↑ "Dementia with grains (argyrophilic grain disease)". Brain Pathology 8 (2): 377–86. April 1998. doi:10.1111/j.1750-3639.1998.tb00161.x. PMID 9546294. 
  25. ↑ "Alpha-synuclein and tau: teammates in neurodegeneration?". Molecular Neurodegeneration 9: 43. October 2014. doi:10.1186/1750-1326-9-43. PMID 25352339. 
  26. ↑ "Extrapyramidal syndromes in frontotemporal degeneration". Journal of Molecular Neuroscience 45 (3): 336–42. November 2011. doi:10.1007/s12031-011-9616-1. PMID 21887521. 
  27. ↑ Esposito, Giuseppe; De Filippis, Daniele; Steardo, Luca; Scuderi, Caterina; Savani, Claudia; Cuomo, Vincenzo; Iuvone, Teresa (2006-09-01). "CB1 receptor selective activation inhibits β-amyloid-induced iNOS protein expression in C6 cells and subsequently blunts tau protein hyperphosphorylation in co-cultured neurons" (in en). Neuroscience Letters 404 (3): 342–346. doi:10.1016/j.neulet.2006.06.012. ISSN 0304-3940. PMID 16837132. https://www.sciencedirect.com/science/article/pii/S0304394006005817. 

External links

Classification



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