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Tau proteins and neurofibrillary degeneration
M Goedert1, M G Spillantini, R A Crowther
1Medical Research Council Laboratory of Molecular Biology, Cambridge, U.K.
Brain Pathology (Zurich, Switzerland)
|July 1, 1991
Summary
Abnormal tau protein phosphorylation drives neurofibrillary pathology in Alzheimer's disease, forming paired helical filaments. This altered tau detaches from microtubules, accumulating in nerve cells and contributing to disease progression.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Paired helical filaments (PHFs) are the primary component of neurofibrillary pathology in Alzheimer's disease (AD).
- Microtubule-associated protein tau (tau) is increasingly recognized as a major constituent of PHFs.
Purpose of the Study:
- To elucidate the role of tau protein in the formation of paired helical filaments in Alzheimer's disease.
- To understand the structural contribution of tau protein domains to the paired helical filament.
Main Methods:
- Accumulation of evidence over three years regarding tau protein's role in PHF formation.
- Analysis of tau protein's binding and phosphorylation status in normal versus Alzheimer's disease brains.
Main Results:
- In normal brain, tau protein binds to axonal microtubules via its tandem repeat region.
- In Alzheimer's disease, tau protein becomes abnormally phosphorylated, detaching from microtubules.
- This detached, phosphorylated tau accumulates to form paired helical filaments, with the tandem repeat region forming the core structure.
Conclusions:
- Abnormal tau phosphorylation is central to neurofibrillary pathology in Alzheimer's disease.
- The tandem repeat region of tau is crucial for the structural integrity of paired helical filaments.
- Altered tau protein dynamics contribute significantly to neuronal dysfunction in Alzheimer's disease.