Neurofibrillary tangles in the context of "Amyloid plaques"

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⭐ Core Definition: Neurofibrillary tangles

Neurofibrillary tangles (NFTs) are intracellular aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer's disease. NFTs also are present in numerous other diseases known collectively as tauopathies. Little is known about their exact relationship to the different pathologies, but it is typically recognized that tauopathy is an important factor in the pathogenesis of several neurodegenerative diseases.

NFTs consist primarily of a misfolded, hyperphosphorylated microtubule-associated protein known as tau, which abnormally polymerizes into insoluble filaments within cells. Under the electron microscope, these polymers of tau are seen to take two basic forms: paired helical filaments (PHFs) and straight filaments. These basic types of tau filaments can vary structurally, especially in different tauopathies. The filaments bundle together to form the neurofibrillary tangles that are evident under the light microscope. Classical NFTs are located within the neuronal cell body, although it is now recognized that abnormal, filamentous tau occurs also in neuronal dendrites and axons (referred to as neuropil threads) and the dystrophic (abnormal) neurites that surround neuritic Abeta plaques. Mature NFTs in cell bodies can have a torch-like or globose appearance, depending on the type of neuron involved. When tangle-containing neurons die, the tangles can remain in the neuropil as extracellular "ghost tangles".

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👉 Neurofibrillary tangles in the context of Amyloid plaques

Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of amyloid beta (Aβ) protein that present mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of microglia and astrocytes can be associated with amyloid plaques. Some plaques occur in the brain as a result of aging, but large numbers of plaques and neurofibrillary tangles are characteristic features of Alzheimer's disease.

The plaques are highly variable in shape and size; in tissue sections immunostained for Aβ, they comprise a log-normal size distribution curve, with an average plaque area of 400–450 square micrometers (μm). The smallest plaques (less than 200 μm), which often consist of diffuse deposits of Aβ, are particularly numerous. Plaques form when Aβ misfolds and aggregates into oligomers and longer polymers, the latter of which are characteristic of amyloid.

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Neurofibrillary tangles in the context of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease and is the most common form of dementia, accounting for around 60–70% of cases. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the average life expectancy following diagnosis is three to twelve years.

The causes of Alzheimer's disease remain poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an allele of apolipoprotein E. Other risk factors include a history of head injury, clinical depression, and high blood pressure. The progression of the disease is largely characterised by the accumulation of malformed protein deposits in the cerebral cortex, called amyloid plaques and neurofibrillary tangles. These misfolded protein aggregates interfere with normal cell function, and over time lead to irreversible degeneration of neurons and loss of synaptic connections in the brain. A probable diagnosis is based on the history of the illness and cognitive testing, with medical imaging and blood tests to rule out other possible causes. Initial symptoms are often mistaken for normal brain aging. Examination of brain tissue is needed for a definite diagnosis, but this can only take place after death.

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LINKED FROM (PARENTS)
← Alzheimer's disease ← Amyloid plaques
LINKS TO (CHILDREN)
Hyperphosphorylated → Tau protein → Biomarker (medicine) → Alzheimer's disease → Tauopathy → Pathogenesis → Neurodegenerative disease → Protein aggregation → Phosphorylation → Microtubule-associated protein → Tau (protein) → Polymer → Protein filament → Electron microscope → Paired helical filament → Light microscope → Cell body → Dendrites → Axons → Neuropil threads → Neurites → Amyloid plaques → Extracellular →