% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{AngladaHuguet:1008614,
      author       = {Anglada-Huguet, Marta and Endepols, Heike and Sydow, Astrid
                      and Hilgers, Ronja and Neumaier, Bernd and Drzezga,
                      Alexander and Kaniyappan, Senthilvelrajan and Mandelkow,
                      Eckhard and Mandelkow, Eva-Maria},
      title        = {{R}eversal of {T}au-{D}ependent {C}ognitive {D}ecay by
                      {B}locking {A}denosine {A}1 {R}eceptors: {C}omparison of
                      {T}ransgenic {M}ouse {M}odels with {D}ifferent {L}evels of
                      {T}auopathy},
      journal      = {International journal of molecular sciences},
      volume       = {24},
      number       = {11},
      issn         = {1422-0067},
      address      = {Basel},
      publisher    = {Molecular Diversity Preservation International},
      reportid     = {FZJ-2023-02431},
      pages        = {9260 -},
      year         = {2023},
      abstract     = {The accumulation of tau is a hallmark of several
                      neurodegenerative diseases and is associatedwith neuronal
                      hypoactivity and presynaptic dysfunction. Oral
                      administration of the adenosineA1 receptor antagonist
                      rolofylline (KW-3902) has previously been shown to reverse
                      spatial memorydeficits and to normalize the basic synaptic
                      transmission in a mouse line expressing
                      full-lengthpro-aggregant tau (TauDK) at low levels, with
                      late onset of disease. However, the efficacy of
                      treatmentremained to be explored for cases of more
                      aggressive tauopathy. Using a combination of
                      behavioralassays, imaging with several PET-tracers, and
                      analysis of brain tissue, we compared the curativereversal
                      of tau pathology by blocking adenosine A1 receptors in three
                      mouse models expressingdifferent types and levels of tau and
                      tau mutants. We show through positron emission
                      tomographyusing the tracer [18F]CPFPX (a selective A1
                      receptor ligand) that intravenous injection of
                      rolofyllineeffectively blocks A1 receptors in the brain.
                      Moreover, when administered to TauDK mice, rolofyllinecan
                      reverse tau pathology and synaptic decay. The beneficial
                      effects are also observed in a line withmore aggressive tau
                      pathology, expressing the amyloidogenic repeat domain of tau
                      (TauRDDK) withhigher aggregation propensity. Both models
                      develop a progressive tau pathology with
                      missorting,phosphorylation, accumulation of tau, loss of
                      synapses, and cognitive decline. TauRDDK causespronounced
                      neurofibrillary tangle assembly concomitant with neuronal
                      death, whereas TauDK accumulatesonly to tau pretangles
                      without overt neuronal loss. A third model tested, the
                      rTg4510line, has a high expression of mutant TauP301L and
                      hence a very aggressive phenotype starting at~3 months of
                      age. This line failed to reverse pathology upon rolofylline
                      treatment, consistent with ahigher accumulation of
                      tau-specific PET tracers and inflammation. In conclusion,
                      blocking adenosineA1 receptors by rolofylline can reverse
                      pathology if the pathological potential of tau remains below
                      athreshold value that depends on concentration and
                      aggregation propensity.},
      cin          = {INM-5 / INM-2},
      ddc          = {540},
      cid          = {I:(DE-Juel1)INM-5-20090406 / I:(DE-Juel1)INM-2-20090406},
      pnm          = {5253 - Neuroimaging (POF4-525) / 5252 - Brain Dysfunction
                      and Plasticity (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5253 / G:(DE-HGF)POF4-5252},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {37298211},
      UT           = {WOS:001005642900001},
      doi          = {10.3390/ijms24119260},
      url          = {https://juser.fz-juelich.de/record/1008614},
}