Assembly of paired helical filaments from mouse tau: implications for the neurofibrillary pathology in transgenic mouse models for Alzheimer's disease

FEBS Letters

Geerts, H.³  Wiech, H.¹  Pangalos, M.²  Kampers, T.¹  Mandelkow, E.¹ 

[1] Max-Planck-Unit for Structural Molecular Biology, Notkestrasse 85, D-22603 Hamburg, Germany;Division of Biotechnology, Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium;Division of Life Sciences, Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium

关键词: Alzheimer's disease;    Microtubule;    Neurofibrillary tangle;    Paired helical filament;    Self assembly;    Tau protein;    AD;    Alzheimer's disease;    APP;    amyloid precursor protein;    MAPs;    microtubule-associated proteins;    NFT;    neurofibrillary tangle;    PHF;    paired helical filament;    ThS;    thioflavin S;   

DOI  :  10.1016/S0014-5793(99)00522-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In Alzheimer's disease and related dementias, human tau protein aggregates into paired helical filaments and neurofibrillary tangles. However, such tau aggregates have not yet been demonstrated in transgenic mouse models of the disease. One of the possible explanations would be that mouse tau has different properties which prevents it from aggregating. We have cloned several murine tau isoforms, containing three or four repeats and different combinations of inserts, expressed them in Escherichia coli and show here that they can all be assembled into paired helical filaments similar to those in Alzheimer's disease, using the same protocols as with human tau. Therefore, the absence of pathologically aggregated tau in transgenic mice cannot be explained by intrinsic differences in mouse tau protein and instead must be explained by other as yet unknown factors.

【 授权许可】

Unknown