Alzheimer’s Tau seeds-induced pathology enhances hippocampal extracellular diffusion
Commun Biol. 2025-11-24; 8(1):
DOI: 10.1038/s42003-025-09054-z
Lire sur PubMed
https://www.bordeaux-neurocampus.fr/12284
Estaún-Panzano J(#)(1), Lovisotto A(#)(1), Mazzocco C(#)(1), Piva C(1), Darricau M(1), Calaresu I(2), Gresil Q(3), Planche V(1), Dehay B(1), Groc L(2), Cognet L(3)(4), Bezard E(5).
Author information:
(1)Univ. Bordeaux, CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France.
(2)Univ. Bordeaux, CNRS, Institut Interdisciplinaire de Neurosciences, UMR 5297,
Bordeaux, France.
(3)Univ. Bordeaux, CNRS, Laboratoire Photonique, Numérique et Nanosciences, UMR
5298, Talence, France.
(4)IOGS, CNRS, Laboratoire Photonique, Numérique et Nanosciences, UMR 5298,
Talence, France.
(5)Univ. Bordeaux, CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France. .
(#)Contributed equally
The extracellular space (ECS) is a complex, dynamic network occupying about 20%
of the brain, filled with a cerebrospinal fluid-like solution rich in
extracellular matrix (ECM) molecules. ECS properties regulate molecular
diffusion, potentially influencing disease-associated protein spread in
neurodegenerative diseases. However, its role in tau propagation remains
unexplored. Using wild-type mice injected with tau seeds purified from
Alzheimer’s disease brain, we applied quantum dot single-particle tracking in
live tissue to examine how tau pathology and inflammation influence
extracellular diffusion. We observed increased diffusion associated with tau
pathology in specific hippocampal regions. Additionally, diffusion profiles
differed between cell-dense and cell-sparse areas. Astrocytes showed abnormal
internalisation of proteoglycans, and matrix structural components were
dysregulated, suggesting a link between altered ECM dynamics and enhanced
diffusion. Increased diffusion and altered ECM dynamics might facilitate the
spread of tau pathology.
© 2025. The Author(s).
DOI: 10.1038/s42003-025-09054-z
PMCID: PMC12644816
PMID: 41286491 [Indexed for MEDLINE]
Conflict of interest statement: Competing interests: E.B. is the Chief
Scientific Officer of Motac Neuroscience Ltd. During the past 3 years, V.P. was
a local unpaid investigator or sub-investigator for clinical trials granted by
NovoNordisk, Biogen, TauRx Pharmaceuticals, Janssen, Green Valley
Pharmaceuticals, and Alector. He received consultant fees for animal studies
from Motac Neuroscience Ltd, outside the submitted work. He received grants from
the Agence Nationale de la Recherche, Fondation Recherche Alzheimer and
Fondation PSP France. All other authors declare no competing interests.