Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms

• Published in: Journal of neurochemistry Vol. 86; no. 3; pp. 582 - 590
• Main Authors: Andorfer, Cathy, Kress, Yvonne, Espinoza, Marisol, De Silva, Rohan, Tucker, Kerry L., Barde, Yves‐Alain, Duff, Karen, Davies, Peter
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.08.2003; Blackwell
• Subjects: Age Factors; aggregation; Alternative Splicing; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Animals; Biological and medical sciences; Brain - metabolism; Brain - pathology; Brain Chemistry; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dendrites - metabolism; Dendrites - pathology; Disease Models, Animal; Humans; Macromolecular Substances; Medical sciences; Mice; Mice, Transgenic; Neurofibrillary Tangles - chemistry; Neurofibrillary Tangles - metabolism; Neurofibrillary Tangles - pathology; Neurology; Neurons - metabolism; Neurons - pathology; non‐mutant tau; Phosphorylation; Protein Isoforms - genetics; Protein Isoforms - metabolism; Reverse Transcriptase Polymerase Chain Reaction; tau Proteins - genetics; tau Proteins - metabolism; transgenic; Nervous system diseases; Phosphorylation; Alzheimer disease; Rodentia; Transgenic animal; Neurofibrillary tangle; Cerebral disorder; Dendrite; Vertebrata; Anatomic pathology; Mammalia; Neuron; Tau protein; Mouse; Central nervous system disease; Degenerative disease; Molecular aggregation; Microtubule; Mutation
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2003.01879.x

Neurofibrillary tangles are composed of insoluble aggregates of the microtubule‐associated protein tau. In Alzheimer's disease the accumulation of neurofibrillary tangles occurs in the absence of tau mutations. Here we present mice that develop pathology from non‐mutant human tau, in the absence of other exogenous factors, including β‐amyloid. The pathology in these mice is Alzheimer‐like, with hyperphosphorylated tau accumulating as aggregated paired helical filaments. This pathologic tau accumulates in the cell bodies and dendrites of neurons in a spatiotemporally relevant distribution.