Tauopathy
Encyclopedia
Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregation of tau protein
in the human brain.
The best known of these illnesses is Alzheimer's disease
(AD), where tau protein is deposited within neuron
s 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 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
.
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.
Other conditions in which neurofibrillary tangles are commonly observed include:
In Pick's disease
and corticobasal degeneration
tau proteins are deposited in the form of inclusion bodies within swollen or "ballooned" neurons. Argyrophilic grain disease (AGD), another type of dementia
, is marked by the presence of abundant argyrophilic grains and coiled bodies on microscopic examination of brain tissue. Some consider it to be a type of Alzheimer disease. It may co-exist with other tauopathies such as progressive supranuclear palsy and corticobasal degeneration.
Some other tauopathies include:
The non-Alzheimer's tauopathies are sometimes grouped together as "Pick's complex".
Tau protein
Tau proteins are proteins that stabilize microtubules. They are abundant in neurons of the central nervous system and are less common elsewhere, but are also expressed at very low levels in CNS astrocytes and oligodendrocytes...
in the human brain.
The best known of these illnesses is Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
(AD), where tau protein is deposited within neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s in the form of neurofibrillary tangles (NFTs). They were first described by the eponymous Alois Alzheimer
Alois Alzheimer
Aloysius "Alois" Alzheimer, was a German psychiatrist and neuropathologist and a colleague of Emil Kraepelin. Alzheimer is credited with identifying the first published case of "presenile dementia", which Kraepelin would later identify as Alzheimer's disease....
in one of his patients suffering from the disorder. Tangles are formed by hyperphosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
of a microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
-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 whether tangles are a primary causative factor in the disease or play a more peripheral role. AD is also classified as an amyloidosis
Amyloidosis
In medicine, amyloidosis refers to a variety of conditions whereby the body produces "bad proteins", denoted as amyloid proteins, which are abnormally deposited in organs and/or tissues and cause harm. A protein is described as being amyloid if, due to an alteration in its secondary structure, it...
because of the presence of senile plaques
Senile plaques
Senile plaques are extracellular deposits of amyloid in the gray matter of the brain. The deposits are associated with degenerative neural structures and an abundance of microglia and astrocytes...
.
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
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
, 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.
Other conditions in which neurofibrillary tangles are commonly observed include:
- Progressive supranuclear palsyProgressive supranuclear palsyProgressive supranuclear palsy is a degenerative disease involving the gradual deterioration and death of specific areas of the brain....
although with straight filament rather than PHF tau - Dementia pugilisticaDementia pugilisticaDementia pugilistica is a type of neurodegenerative disease or dementia, which may affect amateur or professional boxers as well as athletes in other sports who suffer concussions...
(chronic traumatic encephalopathyChronic traumatic encephalopathyChronic traumatic encephalopathy is a progressive degenerative disease found in individuals who have been subjected to multiple concussions and other forms of head injury. A variant of the condition, dementia pugilistica, is primarily associated with boxing...
) - Frontotemporal dementia and parkinsonism linked to chromosome 17Frontotemporal dementia and parkinsonism linked to chromosome 17Frontotemporal dementia and parkinsonism linked to chromosome 17 is an autosomal dominant neurodegenerative disorder, which has three cardinal features: behavioral and personality changes, cognitive impairment, and motor symptoms. FTDP-17 was defined during the International Consensus Conference...
however without detectable β-amyloid plaques. - Lytico-Bodig diseaseLytico-Bodig diseaseLytico-Bodig disease, sometimes spelled Lytigo-bodig is a neurological disease of uncertain aetiology that exists in the United States territory of Guam....
(Parkinson-dementia complex of Guam) - Tangle-predominant dementia, with NFTs similar to AD, but without plaques. Tends to appear in the very old.
- GangliogliomaGangliogliomaGanglioglioma is a tumour that arises from ganglion cells in the central nervous system.The term "gangliocytoma" is sometimes equated with ganglioglioma. However, it is also sometimes equated with ganglioneuroma. In this context, the glial nature of the tumor is de-emphasized...
and gangliocytoma - Meningioangiomatosis
- Subacute sclerosing panencephalitisSubacute sclerosing panencephalitisSubacute sclerosing panencephalitis is a rare chronic, progressive encephalitis that affects primarily children and young adults, caused by a persistent infection of immune resistant measles virus . No cure for SSPE exists, but the condition can be managed by medication if treatment is started at...
- As well as lead encephalopathy, tuberous sclerosisTuberous sclerosisTuberous sclerosis or tuberous sclerosis complex is a rare multi-system genetic disease that causes non-malignant tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin. A combination of symptoms may include seizures, developmental delay, behavioral...
, Hallervorden-Spatz disease, and lipofuscinosis
In Pick's disease
Pick's disease
Pick's disease, is a rare neurodegenerative disease that causes progressive destruction of nerve cells in the brain. Symptoms include loss of speech , and dementia. While some of the symptoms can initially be alleviated, the disease progresses and patients often die within two to ten years...
and corticobasal degeneration
Corticobasal degeneration
Corticobasal degeneration or Corticobasal Ganglionic Degeneration is a rare progressive neurodegenerative disease involving the cerebral cortex and the basal ganglia. It is characterized by marked disorders in movement and cognitive dysfunction...
tau proteins are deposited in the form of inclusion bodies within swollen or "ballooned" neurons. Argyrophilic grain disease (AGD), another type of dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
, is marked by the presence of abundant argyrophilic grains and coiled bodies on microscopic examination of brain tissue. Some consider it to be a type of Alzheimer disease. It may co-exist with other tauopathies such as progressive supranuclear palsy and corticobasal degeneration.
Some other tauopathies include:
- Frontotemporal dementiaFrontotemporal dementiaFrontotemporal dementia is a clinical syndrome caused by degeneration of the frontal lobe of the brain and may extend back to the temporal lobe...
- Frontotemporal lobar degenerationFrontotemporal lobar degeneration-Further reading:*Hodges, John R. The Frontotemporal Dementia Syndromes. Cambridge University Press. 2007 ISBN 978-0-521-85477-1-External links:****Mayo Clinic - **...
The non-Alzheimer's tauopathies are sometimes grouped together as "Pick's complex".
External links
- Pathologic page about Neurofibrillary tangles, by the University of Oklahoma.
- http://www.lifesci.sussex.ac.uk/home/Julian_Thorpe/ad_cyto.htm#tau