Related Experiment Video
Updated: May 30, 2026
09:22
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
Pathogenesis of the tauopathies
Michel Goedert1, Maria Grazia Spillantini
1MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK. mg@mrc-lmb.cam.ac.uk
Journal of Molecular Neuroscience : MN
|July 26, 2011
Summary
Microtubule-associated protein tau (tau) misfolding causes neurodegenerative diseases like frontotemporal dementia. Evidence suggests multiple tau protein structures (conformers) contribute to disease diversity.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Microtubule-associated protein tau (tau) is implicated in neurodegenerative diseases.
- Tau protein misfolding, hyperphosphorylation, and filament formation are hallmarks of tauopathies.
- Mutations in the MAPT gene explain a subset of frontotemporal dementia cases, demonstrating tau's role in neurodegeneration.
Purpose of the Study:
- To explore the role of tau protein dysfunction in neurodegenerative diseases.
- To investigate the heterogeneity observed in tauopathies despite conserved hyperphosphorylation sites.
- To provide experimental support for the concept of distinct tau conformers.
Main Methods:
- Analysis of MAPT gene mutations in frontotemporal dementia.
- Comparative analysis of hyperphosphorylated tau sites across different tauopathies.
- Investigation of tau filament morphologies and isoform compositions.
- Experimental validation of multiple tau conformers.
Main Results:
- MAPT mutations are linked to frontotemporal dementia and parkinsonism.
- Similar hyperphosphorylation sites exist across tauopathies, yet filament structures and tau isoforms differ.
- Experimental data support the existence of multiple tau conformers.
Conclusions:
- Tau protein dysfunction is sufficient to cause neurodegeneration and dementia.
- The variability in tauopathies suggests the involvement of different tau conformers.
- Understanding tau conformers is crucial for deciphering tauopathy pathogenesis.
Related Concept Videos
01:23Alzheimer Disease ll: Pathophysiology
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
01:24Parkinson Disease ll: Pathophysiology
Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:22Dementia l: Introduction
Dementia is an acquired, progressive syndrome characterized by a decline in multiple cognitive domains severe enough to impair daily functioning and reduce independence. Although memory loss is a central feature, the diagnosis requires additional deficits involving language, executive function, visuospatial skills, judgment, calculation, or abstract reasoning. These cognitive impairments reflect underlying neurodegenerative or vascular processes that gradually disrupt neuronal networks...
01:26Alzheimer's Disease: Overview
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...