Cerebrospinal fluid from Alzheimer’s disease patients promotes tau aggregation in transgenic mice

Zhiva Skachokova†,
Alfonso Martinisi†,
Martin Flach,
Frederik Sprenger,
Yvonne Naegelin,
Viviane Steiner-Monard,
Marc Sollberger,
Andreas U. Monsch,
Michel Goedert,
Markus Tolnay and
David T. WinklerEmail author View ORCID ID profile

†Contributed equally

Acta Neuropathologica Communications20197:72

https://doi.org/10.1186/s40478-019-0725-3

Received: 14 March 2019
Accepted: 17 April 2019
Published: 7 May 2019

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.