Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils.
beta-Amyloid plaques and neurofibrillary tangles (NFTs) are the defining neuropathological hallmarks of Alzheimer's disease, but their pathophysiological relation is unclear. Injection of beta-amyloid Abeta42 fibrils into the brains of P301L mutant tau transgenic mice caused fivefold increases in the numbers of NFTs in cell bodies within the amygdala from where neurons project to the injection sites. Gallyas silver impregnation identified NFTs that contained tau phosphorylated at serine 212/threonine 214 and serine 422. NFTs were composed of twisted filaments and occurred in 6-month-old mice as early as 18 days after Abeta42 injections. Our data support the hypothesis that Abeta42 fibrils can accelerate NFT formation in vivo.
Götz
J
J
Division of Psychiatry Research, University of Zürich, August Forel Strasse 1, 8008 Zürich, Switzerland. goetz@bli.unizh.ch
Chen
F
F
van Dorpe
J
J
Nitsch
R M
RM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000679:Amygdala / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000473:pathology*; D000939:Epitopes; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism*; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D011487:Protein Conformation; D020033:Protein Isoforms; D012727:Sex Characteristics; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000939:Epitopes; D010446:Peptide Fragments; D020033:Protein Isoforms; C075222:amyloid beta-protein (1-42); D016875:tau Proteins