Tauopathy

Diagram of a normal microtubule and one affected by tauopathy

Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregation of tau protein^[1] in the human brain.

The best-known of these illnesses is Alzheimer's disease (AD), wherein tau protein is deposited within neurons in the form of neurofibrillary tangles (NFTs). They were first described by the eponymous Alois Alzheimer in one of his patients suffering from the disorder. Tangles are formed by hyperphosphorylation of a microtubule-associated protein known as tau, causing it to aggregate in an insoluble form. (These aggregations of hyperphosphorylated tau protein are also referred to as PHF, or "paired helical filaments"). The precise mechanism of tangle formation is not completely understood, and it is still controversial as to whether tangles are a primary causative factor in the disease or play a more peripheral role. AD is also classified as an amyloidosis because of the presence of senile plaques.^[2]

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's 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.^[3]

Other conditions in which neurofibrillary tangles are commonly observed include:

• Progressive supranuclear palsy^[4] although with straight filament rather than PHF tau
• Dementia pugilistica (chronic traumatic encephalopathy)^[5]
• Frontotemporal dementia and parkinsonism linked to chromosome 17, however without detectable β-amyloid plaques.^[6]
• Lytico-Bodig disease (Parkinson-dementia complex of Guam)^[7]
• Tangle-predominant dementia, with NFTs similar to AD, but without plaques. Tends to appear in the very old.^[2][8][9]
• Ganglioglioma and gangliocytoma^[10]
• Meningioangiomatosis^[11]
• Subacute sclerosing panencephalitis^[12]
• As well as lead encephalopathy, tuberous sclerosis, Hallervorden-Spatz disease, and lipofuscinosis^[13]

In Pick's disease and corticobasal degeneration tau proteins are deposited in the form of inclusion bodies within swollen or "ballooned" neurons.^[14]

Argyrophilic grain disease (AGD), another type of dementia,^[15][16][17] is marked by the presence of abundant argyrophilic grains and coiled bodies on microscopic examination of brain tissue.^[18] Some consider it to be a type of Alzheimer disease.^[18] It may co-exist with other tauopathies such as progressive supranuclear palsy and corticobasal degeneration,^[2] and also Pick's disease.^[19]

Huntington's disease: a neurodegenerative disease caused by a CAG tripled expansion in huntingtin gene is the most recently described tauopathy (Fernandez-Nogales et al. Nat Med 2014). JJ Lucas and co-workers demonstrated that in HD brains tau levels are increased and that the 4R/3R balance is altered. In addition, in this study, JJ Lucas shows intranuclear insoluble deposits of tau. These "Lucas rods" were also found in Alzheimer's disease brains.

Tauopathies, most notably Alzheimer's, often have overlap with synucleinopathies, possibly because of interaction between the synuclein and tau proteins.^[20][21]

The non-Alzheimer's tauopathies are sometimes grouped together as "Pick's complex" because of their association with Frontotemporal dementia, or Frontotemporal lobar degeneration.^[22][23][24]

See also

• Proteopathy

References

External links

• Delacourte, A (2005). "Tauopathies: recent insights into old diseases". Folia Neuropathologica 43 (4): 244–57. PMID 16416389. 
• http://www.lifesci.sussex.ac.uk/home/Julian_Thorpe/ad_cyto.htm#tau
• Buée, L; Delacourte, A (1999). "Comparative biochemistry of tau in progressive supranuclear palsy, corticobasal degeneration, FTDP-17 and Pick's disease". Brain Pathology 9 (4): 681–93. doi:10.1111/j.1750-3639.1999.tb00550.x. PMID 10517507.