Amyloid-induced neurofibrillary tangle formation in Alzheimer's disease: insight from transgenic mouse and tissue-culture models

Gotz, Juergen, Schild, Andreas, Hoerndli, Fred and Pennanen, Luis (2004) Amyloid-induced neurofibrillary tangle formation in Alzheimer's disease: insight from transgenic mouse and tissue-culture models. International Journal of Developmental Neuroscience, 22 7: 453-465. doi:10.1016/j.ijdevneu.2004.07.013


Author Gotz, Juergen
Schild, Andreas
Hoerndli, Fred
Pennanen, Luis
Title Amyloid-induced neurofibrillary tangle formation in Alzheimer's disease: insight from transgenic mouse and tissue-culture models
Journal name International Journal of Developmental Neuroscience   Check publisher's open access policy
ISSN 0736-5748
1873-474X
Publication date 2004-11-01
Sub-type Article (original research)
DOI 10.1016/j.ijdevneu.2004.07.013
Open Access Status Not yet assessed
Volume 22
Issue 7
Start page 453
End page 465
Total pages 13
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon Press
Collection year 2014
Language eng
Abstract Of all forms of dementia, Alzheimer's disease is the most prevalent. It is histopathologically characterized by β-amyloid-containing plaques, tau-containing neurofibrillary tangles, reduced synaptic density and neuronal loss in selected brain areas. For the rare familial forms of Alzheimer's disease, pathogenic mutations have been identified in both the gene encoding the precursor of the Aβ peptide, APP, itself and in the presenilin genes which encode part of the APP-protease complex. For the more frequent sporadic forms of Alzheimer's disease, the pathogenic trigger has not been unambiguously identified. Whether Aβ is again the main cause remains to be heavily discussed. In a related disorder termed frontotemporal dementia, which is characterized by tangles in the absence of β-amyloid deposition, mutations have been identified in tau which also lead to neurodegeneration and dementia. For Alzheimer's disease the existence of familial forms lead to the proposition of the amyloid cascade hypothesis, which claims that β-amyloid causes or enhances the tangle pathology. In this review, we describe tau transgenic mouse models in which aspects of the tau-associated pathology, including tangle formation, has been achieved. Moreover, tau transgenic mouse and tissue-culture models were used to test the amyloid cascade hypothesis. In addition, we discuss alternative hypotheses to explain the sporadic forms. The animal and tissue-culture models will provide insight into the underlying biochemical mechanisms of tau aggregation and nerve cell degeneration. These mechanisms may be partially shared between sporadic Alzheimer's disease, the familial forms and frontotemporal dementia. Eventually, Alzheimer's disease may be redefined based on biochemical events rather than phenotype.
Keyword Alzheimer's disease
Amyloid
Neurofibrillary tangles
SH-SY5Y cells
Tau
Transgenic
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Ageing Dementia Research Publications
 
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