Tauopathy belongs to a class of

neurodegenerative disease A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

s involving the aggregation of

tau protein The tau proteins (abbreviated from tubulin associated unit) are a group of six highly soluble protein isoforms produced by alternative splicing from the gene ''MAPT'' (microtubule-associated protein tau). They have roles primarily in maintaining ...

into neurofibrillary or gliofibrillary tangles in the human brain. Tangles are formed by

hyperphosphorylation Hyperphosphorylation occurs when a biochemical with multiple phosphorylation sites is fully saturated. Hyperphosphorylation is one of the signaling mechanisms used by the cell to regulate mitosis. When these mechanisms fail, developmental problems ...

of the

microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...

protein known as tau, causing the protein to dissociate from microtubules and form insoluble aggregates. (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 Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

or play a peripheral role is unknown.

Detection and imaging

;Post-mortem: Tau tangles are seen microscopically in stained brain samples. ;Pre-mortem: In living patients tau tangle locations can be imaged with a

PET scan Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...

using a suitable radio-emissive agent.

Alzheimer's disease

Neurofibrillary tangles were first described by

Alois Alzheimer Alois Alzheimer ( , , ; 14 June 1864 – 19 December 1915) 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 Kraepel ...

in one of his patients with

(AD). The tangles are considered a secondary tauopathy. AD is also classified as an

amyloidosis Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weight ...

because of the presence of

senile plaques Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of micr ...

. When tau becomes hyperphosphorylated, the protein dissociates from the microtubules in axons. Then, tau becomes misfolded and the protein begins to aggregate, which eventually forms the neurofibrillary tangles seen in Alzheimer's patients. 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. 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 The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''Ps ...

regions such as the

hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...

, and V and VI when there's extensive neocortical involvement. This should not be confused with the degree of

senile plaque Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of mi ...

involvement, which progresses differently.

Other diseases

Primary age-related tauopathy Primary age-related tauopathy (PART) is a neuropathological designation introduced in 2014 to describe the neurofibrillary tangles (NFT) that are commonly observed in the brains of normally aged and cognitively impaired individuals that can occur ...

(PART) dementia, with NFTs similar to AD, but without

amyloid plaques Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of micr ...

. *

Chronic traumatic encephalopathy Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repeated trauma to the head. The encephalopathy symptoms can include behavioral problems, mood problems, and problems with thinking. The disease often gets worse o ...

(CTE) *

Progressive supranuclear palsy Progressive supranuclear palsy (PSP) is a late-onset degenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty ...

(PSP) *

Corticobasal degeneration Corticobasal degeneration (CBD) is a rare neurodegenerative disease involving the cerebral cortex and the basal ganglia. CBD symptoms typically begin in people from 50 to 70 years of age, and the average disease duration is six years. It is chara ...

(CBD) *

Frontotemporal dementia and parkinsonism linked to chromosome 17 Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is an autosomal dominant neurodegenerative tauopathy and Parkinson plus syndrome. FTDP-17 is caused by mutations in the MAPT (microtubule associated protein tau) gene loca ...

(FTDP-17) * Vacuolar tauopathy *

Lytico-bodig disease Lytico-bodig (also Lytigo-bodig) disease, Guam disease, or amyotrophic lateral sclerosis-parkinsonism-dementia (ALS-PDC) is a neurodegenerative disease of uncertain etiology endemic to the Chamorro people of the island of Guam in Micronesia. ''Ly ...

(Parkinson-dementia complex of Guam) *

Ganglioglioma Ganglioglioma is a rare, slow-growing primary central nervous system (CNS) tumor which most frequently occurs in the temporal lobes of children and young adults Classification Gangliogliomas are generally benign WHO grade I tumors; the presence o ...

and

gangliocytoma Ganglioglioma is a rare, slow-growing primary central nervous system (CNS) tumor which most frequently occurs in the temporal lobes of children and young adults Classification Gangliogliomas are generally benign WHO grade I tumors; the presence o ...

* Meningioangiomatosis *

Postencephalitic parkinsonism Post-encephalitic parkinsonism is a disease believed to be caused by a viral illness that triggers degeneration of the nerve cells in the substantia nigra. Overall, this degeneration leads to clinical parkinsonism. Historically, starting in 1917 a ...

Subacute sclerosing panencephalitis Subacute sclerosing panencephalitis (SSPE)—also known as Dawson disease—is a rare form of chronic, progressive brain inflammation caused by slow infection with certain defective strains of hypermutated measles virus. The condition primarily ...

(SSPE) * As well as

lead encephalopathy Toxic encephalopathy is a neurologic disorder caused by exposure to neurotoxic organic solvents such as toluene, following exposure to heavy metals such as manganese, as a side effect of melarsoprol treatment for African trypanosomiasis, adverse e ...

tuberous sclerosis Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination ...

Pantothenate kinase-associated neurodegeneration Pantothenate kinase-associated neurodegeneration (PKAN), formerly called Hallervorden–Spatz syndrome, is a genetic degenerative disease of the brain that can lead to parkinsonism, dystonia, dementia, and ultimately death. Neurodegeneration in P ...

, and lipofuscinosis In both

Pick's disease Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of frontal and temporal lobes. FTDs broadly present as ...

and

corticobasal degeneration Corticobasal degeneration (CBD) is a rare neurodegenerative disease involving the cerebral cortex and the basal ganglia. CBD symptoms typically begin in people from 50 to 70 years of age, and the average disease duration is six years. It is chara ...

, tau proteins are deposited as

inclusion bodies Inclusion bodies are aggregates of specific types of protein found in neurons, a number of tissue cells including red blood cells, bacteria, viruses, and plants. Inclusion bodies of aggregations of multiple proteins are also found in muscle cells ...

within swollen or "ballooned" neurons. Argyrophilic grain disease (AGD), another type of

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

, is marked by an abundance of argyrophilic grains and coiled bodies upon microscopic examination of brain tissue. Some consider it to be a type of

. It may co-exist with other tauopathies such as progressive supranuclear palsy and corticobasal degeneration, and also Pick's disease. Tauopathies are often overlapped with

synucleinopathies Synucleinopathies (also called α-Synucleinopathies) are neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibres or glial cells. There are three main types of synucle ...

, possibly due to interaction between the synuclein and tau proteins. The non-Alzheimer's tauopathies are sometimes grouped together as "Pick's complex" due to their association with

frontotemporal dementia Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of frontal and temporal lobes. FTDs broadly present as ...

, or

frontotemporal lobar degeneration Frontotemporal lobar degeneration (FTLD) is a pathological process that occurs in frontotemporal dementia. It is characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes. Common ...

References

External links

{{Cytoskeletal defects Dementia Medical signs Histopathology Cytoskeletal defects

Detection and imaging

Alzheimer's disease

Other diseases

See also

References

External links