Phosphorylation of Tau at S422 is enhanced by Abeta in TauPS2APP triple transgenic mice.
Amyloid beta peptides and microtubule-associated protein Tau are misfolded and form aggregates in brains of Alzheimer's disease patients. To examine their specific roles in the pathogenesis of Alzheimer's disease and their relevance in neurodegenerative processes, we have created TauPS2APP triple transgenic mice that express human mutated Amyloid Precursor Protein, presenilin 2 and Tau. We present a cross-sectional analysis of these mice at 4, 8, 12 and 16 months of age. By comparing with single transgenic Tau mice, we demonstrate that accumulation of Abeta in TauPS2APP triple transgenic mice impacts on Tau pathology by increasing the phosphorylation of Tau at serine 422, as determined by a novel immunodetection method that is able to reliably measure phospho-Tau species in transgenic mouse brains. The TauPS2APP triple transgenic mouse model will be very useful for studying the effect of new therapeutic paradigms on amyloid deposition and downstream neurofibrillary tangle development.
F. Hoffmann-La-Roche Ltd, Pharmaceutical Research Neuroscience, Basel, Switzerland.
Fiona
F
Grueninger
Bernd
B
Bohrmann
Christian
C
Czech
Theresa Maria
TM
Ballard
Johann R
JR
Frey
Claudia
C
Weidensteiner
Markus
M
von Kienlin
Laurence
L
Ozmen
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000378:metabolism; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism; D053766:Presenilin-2 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D005819:Genetic Markers; D053766:Presenilin-2; D016875:tau Proteins