% 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{Schneeberger:299828,
author = {S. Schneeberger and S. J. Kim and M. N. Geesdorf and E.
Friebel and P. Eede and M. Jendrach and A. Boltengagen and
C. Braeuning and T. Ruhwedel and A. J. Hülsmeier and N.
Gimber and M. Foerster and J. Obst and M. Andreadou and S.
Mundt and J. Schmoranzer and S. Prokop and W. Kessler and T.
Kuhlmann and W. Möbius and K.-A. Nave and T. Hornemann and
B. Becher and J. M. Edgar and N. Karaiskos and C. Kocks and
N. Rajewsky$^*$ and F. L. Heppner},
title = {{I}nterleukin-12 signaling drives {A}lzheimer's disease
pathology through disrupting neuronal and oligodendrocyte
homeostasis.},
journal = {Nature aging},
volume = {5},
number = {4},
issn = {2662-8465},
address = {London},
publisher = {Nature Research},
reportid = {DKFZ-2025-00565},
pages = {622-641},
year = {2025},
note = {2025 Apr;5(4):622-641},
abstract = {Neuroinflammation including interleukin
(IL)-12/IL-23-signaling is central to Alzheimer's disease
(AD) pathology. Inhibition of p40, a subunit of IL-12/IL-23,
attenuates pathology in AD-like mice; however, its signaling
mechanism and expression pattern remained elusive. Here we
show that IL-12 receptors are predominantly expressed in
neurons and oligodendrocytes in AD-like APPPS1 mice and in
patients with AD, whereas IL-23 receptor transcripts are
barely detectable. Consistently, deletion of the IL-12
receptor in neuroectodermal cells ameliorated AD pathology
in APPPS1 mice, whereas removal of IL-23 receptors had no
effect. Genetic ablation of IL-12 signaling alone reverted
the loss of mature oligodendrocytes, restored myelin
homeostasis, rescued the amyloid-β-dependent reduction of
parvalbumin-positive interneurons and restored
phagocytosis-related changes in microglia of APPPS1 mice.
Furthermore, IL-12 protein expression was increased in human
AD brains compared to healthy age-matched controls, and
human oligodendrocyte-like cells responded profoundly to
IL-12 stimulation. We conclude that oligodendroglial and
neuronal IL-12 signaling, but not IL-23 signaling, are key
in orchestrating AD-related neuroimmune crosstalk and that
IL-12 represents an attractive therapeutic target in AD.},
cin = {BE01},
ddc = {610},
cid = {I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40082619},
doi = {10.1038/s43587-025-00816-2},
url = {https://inrepo02.dkfz.de/record/299828},
}