Neurofibrillary tangle

Microscopy of a cell with neurofibrillary tangles (marked by arrows).
Diagram of how microtubules disintegrate with Alzheimer's disease
Overview of RNA interference.

Neurofibrillary tangles (NFTs) are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer's disease.

- Neurofibrillary tangle
Microscopy of a cell with neurofibrillary tangles (marked by arrows).

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Diagram of a normal microtubule and one affected by tauopathy

Tauopathy

Diagram of a normal microtubule and one affected by tauopathy
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).

Tauopathy belongs to a class of neurodegenerative diseases involving the aggregation of tau protein into neurofibrillary or gliofibrillary tangles (Neurofibrillary tangle) in the human brain.

Drawing comparing a normal aged brain (left) and the brain of a person with Alzheimer's. Characteristics that separate the two are pointed out.

Alzheimer's disease

Neurodegenerative disease that usually starts slowly and progressively worsens.

Neurodegenerative disease that usually starts slowly and progressively worsens.

Drawing comparing a normal aged brain (left) and the brain of a person with Alzheimer's. Characteristics that separate the two are pointed out.
Stages of atrophy in Alzheimer's.
A normal brain on the left and a late-stage Alzheimer's brain on the right
In Alzheimer's disease, changes in tau protein lead to the disintegration of microtubules in brain cells.
Histopathologic images of Alzheimer's disease, in the CA3 area of the hippocampus, showing an amyloid plaque (top right), neurofibrillary tangles (bottom left), and granulovacuolar degeneration bodies (bottom center)
PET scan of the brain of a person with Alzheimer's disease showing a loss of function in the temporal lobe
Cognitive tests such as the Mini–Mental State Examination (MMSE) can help in the diagnosis of Alzheimer's disease. In this test instructions are given to copy drawings like the one shown, remember some words, read, and subtract numbers serially.
Intellectual activities such as playing chess or regular social interaction have been linked to a reduced risk of Alzheimer's disease in epidemiological studies, although no causal relationship has been found.
Three-dimensional molecular model of donepezil, an acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease symptoms
Molecular structure of memantine, a medication approved for advanced Alzheimer's disease symptoms
Alois Alzheimer's patient Auguste Deter in 1902. Hers was the first described case of what became known as Alzheimer's disease.
Self-portrait of artist William Utermohlen, created after Alzheimer's disease diagnosis

The disease process is largely associated with amyloid plaques, neurofibrillary tangles, and loss of neuronal connections in the brain.

Image of a man diagnosed with dementia in the 1800s

Dementia

Damaged by injury or disease.

Damaged by injury or disease.

Image of a man diagnosed with dementia in the 1800s
A drawing of a woman diagnosed with dementia
A drawing of an old man diagnosed with senile dementia
Brain atrophy in severe Alzheimer's
Donepezil
Deaths per million persons in 2012 due to dementia
Disability-adjusted life year for Alzheimer and other dementias per 100,000 inhabitants in 2004.
Woman with dementia being cared for at home in Ethiopia

High proportions of viral-associated proteins in amyloid plaques or neurofibrillary tangles (NFTs) confirm the involvement of HSV-1 in Alzheimer's disease pathology.

Neurons were grown in tissue culture and stained with antibody to MAP2 protein in green and MAP tau in red using the immunofluorescence technique. MAP2 is found only in dendrites and perikarya, while tau is found not only in the dendrites and perikarya but also in axons. As a result, axons appear red while the dendrites and perikarya appear yellow, due to superimposition of the red and green signals. DNA is shown in blue using the DAPI stain which highlights the nuclei. Image courtesy EnCor Biotechnology Inc.

Tau protein

The tau proteins (or τ proteins, after the Greek letter with that name) are a group of six highly soluble protein isoforms produced by alternative splicing from the gene MAPT (microtubule-associated protein tau).

The tau proteins (or τ proteins, after the Greek letter with that name) are a group of six highly soluble protein isoforms produced by alternative splicing from the gene MAPT (microtubule-associated protein tau).

Neurons were grown in tissue culture and stained with antibody to MAP2 protein in green and MAP tau in red using the immunofluorescence technique. MAP2 is found only in dendrites and perikarya, while tau is found not only in the dendrites and perikarya but also in axons. As a result, axons appear red while the dendrites and perikarya appear yellow, due to superimposition of the red and green signals. DNA is shown in blue using the DAPI stain which highlights the nuclei. Image courtesy EnCor Biotechnology Inc.

Pathologies and dementias of the nervous system such as Alzheimer's disease and Parkinson's disease are associated with tau proteins that have become hyperphosphorylated insoluble aggregates called neurofibrillary tangles.

Amyloid beta immunostaining showing amyloid plaques (brown).

Amyloid plaques

Amyloid plaques (also known as neuritic plaques, Aβ plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain.

Amyloid plaques (also known as neuritic plaques, Aβ plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain.

Amyloid beta immunostaining showing amyloid plaques (brown).
Two amyloid plaques from the brain of a patient with Alzheimer's disease. In this photomicrograph, neurites are darkly stained with the Naoumenko-Feigin silver method, and the pink elements (including the plaque cores) are stained with the periodic acid-Schiff (PAS) counterstain. The bar is 20 microns (0.02 mm) in length.

Some plaques occur in the brain as a result of senescence (aging), but large numbers of plaques and neurofibrillary tangles are characteristic features of Alzheimer's disease.

A normal brain (left) and one with CTE (right)

Chronic traumatic encephalopathy

Neurodegenerative disease linked to repeated trauma to the head.

Neurodegenerative disease linked to repeated trauma to the head.

A normal brain (left) and one with CTE (right)

Supporting features of CTE are: superficial neurofibrillary tangles (NFTs); p–tau in CA2 and CA4 hippocampus; p-tau in: mammillary bodies, hypothalamic nuclei, amygdala, nucleus accumbens, thalamus, midbrain tegmentum, nucleus basalis of Meynert, raphe nuclei, substantia nigra and locus coeruleus; p-tau thorn-shaped astrocytes (TSA) in the subpial region; p-tau dot-like neurites.

A person with progressive dementia, ataxia, and incontinence. A clinical diagnosis of normal-pressure hydrocephalus was entertained. Imaging did not support this, however, and on formal testing, abnormal nystagmus and eye movements were detected. A sagittal view of the CT/MRI scan shows atrophy of the midbrain, with preservation of the volume of the pons. This appearance has been called the "hummingbird sign" or "penguin sign". Also, atrophy of the tectum is seen, particularly the superior colliculi. These findings suggest the diagnosis of progressive supranuclear palsy.

Progressive supranuclear palsy

Late-onset degenerative disease involving the gradual deterioration and death of specific volumes of the brain.

Late-onset degenerative disease involving the gradual deterioration and death of specific volumes of the brain.

A person with progressive dementia, ataxia, and incontinence. A clinical diagnosis of normal-pressure hydrocephalus was entertained. Imaging did not support this, however, and on formal testing, abnormal nystagmus and eye movements were detected. A sagittal view of the CT/MRI scan shows atrophy of the midbrain, with preservation of the volume of the pons. This appearance has been called the "hummingbird sign" or "penguin sign". Also, atrophy of the tectum is seen, particularly the superior colliculi. These findings suggest the diagnosis of progressive supranuclear palsy.

The neurons display neurofibrillary tangles (NFTs), which are clumps of tau protein, a normal part of a brain cell's internal structural skeleton.

Micrograph of a vasculitic neuropathy. Plastic embedded. Toluidine blue stain.

Primary age-related tauopathy

Micrograph of a vasculitic neuropathy. Plastic embedded. Toluidine blue stain.

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 independently of the amyloid plaques of Alzheimer's disease (AD).

Surface representation of Ubiquitin.

Ubiquitin

Small regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ubiquitously.

Small regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ubiquitously.

Surface representation of Ubiquitin.
The ubiquitylation system (showing a RING E3 ligase).
Diagram of lysine 48-linked diubiquitin. The linkage between the two ubiquitin chains is shown in orange.
Diagram of lysine 63-linked diubiquitin. The linkage between the two ubiquitin chains is shown in orange.

Neurofibrillary tangles in Alzheimer's disease

Normal brain on left contrasted with structural changes shown in brain on right of person with Alzheimer's disease, the most common neurodegenerative disease.

Lytico-bodig disease

Neurodegenerative disease of uncertain etiology endemic to the Chamorro people of the island of Guam in Micronesia.

Neurodegenerative disease of uncertain etiology endemic to the Chamorro people of the island of Guam in Micronesia.

Normal brain on left contrasted with structural changes shown in brain on right of person with Alzheimer's disease, the most common neurodegenerative disease.

During autopsies, neurofibrillary tangles are found in the brain which are congruent to the brain of an Alzheimer's patient.