Abstract
A pathological pathway leading from soluble, monomeric to insoluble, filamentous Tau, is believed to underlie human Tauopathies. Cases of frontotemporal dementia are caused by dominantly inherited mutations in MAPT, the Tau gene. They show that dysfunction of Tau protein is sufficient to cause neurodegeneration and dementia. Extrapolation to the more common sporadic Tauopathies leads one to conclude that the pathological pathway is central to the development of all cases of disease, even if there are multiple reasons for Tau assembly. These findings are conceptually similar to those reported for beta-amyloid, alpha-synuclein and prion protein. Here, we provide an overview of Tau filaments and their positron emission tomography ligands.
Highlights
Neurofibrillary lesions strongly correlate with cognitive deficits, making them an important therapeutic target for Alzheimer’s disease (AD) [1, 2]
Cryogenic electron microscopy is bound to provide atomic structures of Tau bound to microtubules that were assembled from tubulin in different ways [34]
MAPT mutations account for approximately 5% of cases of frontotemporal dementia and are concentrated in exons 9–12 and the introns flanking exon 10
Summary
Cases of frontotemporal dementia are caused by dominantly inherited mutations in MAPT, the Tau gene. They show that dysfunction of Tau protein is sufficient to cause neurodegeneration and dementia. Extrapolation to the more common sporadic Tauopathies leads one to conclude that the pathological pathway is central to the development of all cases of disease, even if there are multiple reasons for Tau assembly. These findings are conceptually similar to those reported for beta-amyloid, alpha-synuclein and prion protein.
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