The neuritic plaque facilitates pathological conversion of tau in an Alzheimer's disease mouse model.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27373369.
- Also identified by DOI 10.1038/ncomms12082 and PMC identifier 4932197.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
A central question in Alzheimer's Disease (AD) is whether the neuritic plaque is necessary and sufficient for the development of tau pathology. Hyperphosphorylation of tau is found within dystrophic neurites surrounding β-amyloid deposits in AD mouse models but the pathological conversion of tau is absent. Likewise, expression of a human tau repeat domain in mice is insufficient to drive the pathological conversion of tau. Here we developed an Aβ-amyloidosis mouse model that expresses the human tau repeat domain and show that in these mice, the neuritic plaque facilitates the pathological conversion of wild-type tau. We show that this tau fragment seeds the neuritic plaque-dependent pathological conversion of wild-type tau that spreads from the cortex and hippocampus to the brain stem. These results establish that in addition to the neuritic plaque, a second determinant is required to drive the conversion of wild-type tau.
Medical subject headings
- Alzheimer Disease
- Neurites
- Plaque, Amyloid
- tau Proteins