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Cerebrospinal fluid from Alzheimer's disease patients promotes tau aggregation in transgenic mice
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 4523871
Author(s) Skachokova, Zhiva; Martinisi, Alfonso; Flach, Martin; Sprenger, Frederik; Naegelin, Yvonne; Steiner-Monard, Viviane; Sollberger, Marc; Monsch, Andreas U.; Goedert, Michel; Tolnay, Markus; Winkler, David T.
Author(s) at UniBasel Monsch, Andreas U.
Year 2019
Title Cerebrospinal fluid from Alzheimer's disease patients promotes tau aggregation in transgenic mice
Journal Acta neuropathologica communications
Volume 7
Number 1
Pages / Article-Number 72
Keywords Alzheimer’s disease; Cerebrospinal fluid; Neurodegeneration; Prion; Seeding; Tau; Transgenic mouse models
Mesh terms Aged; Aged, 80 and over; Alzheimer Disease, cerebrospinal fluid; Animals; Cognitive Dysfunction, cerebrospinal fluid; Hippocampus, pathology; Humans; Mice, Transgenic; Middle Aged; Neurons, pathology; Protein Aggregation, Pathological, pathology; tau Proteins, administration & dosage
Abstract Tau is a microtubule stabilizing protein that forms aggregates in Alzheimer's disease (AD). Tau derived from AD patients' brains induces tau aggregation in a prion-like manner when injected into susceptible mouse models.Here we investigated whether cerebrospinal fluid (CSF) collected from patients diagnosed with probable AD or mild cognitive impairment (MCI) likely due to AD harbors a prion-like tau seeding potential. CSF was injected intrahippocampally into young P301S tau transgenic mice. CSF obtained from AD or MCI patients increased hippocampal tau hyperphosphorylation and tau tangle formation in these mice at 4 months post-seeding. Tau pathology was also accentuated in the contralateral hippocampus, and in anterior and posterior directions, indicative of spreading.We provide first evidence for in vivo prion-like properties of AD patients' CSF, accelerating tau pathology in susceptible tau transgenic mice. This demonstrates that biologically active tau seeds reach the CSF compartment in AD. Further studies may help to evaluate strain specific properties of CSF derived tau bioseeds, and to assess their diagnostic potential. What do you want to do ? New mail Copy
Publisher BioMed Central
ISSN/ISBN 2051-5960
edoc-URL https://edoc.unibas.ch/79873/
Full Text on edoc No
Digital Object Identifier DOI 10.1186/s40478-019-0725-3
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/31064413
ISI-Number WOS:000467529000001
Document type (ISI) Journal Article
 
   

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