Axonal Branch Points of Parvalbumin Interneurons are Focal Sites of Tau-Induced Degeneration
- 1Institute of Neuropathology, LMU Medizin, Ludwig Maximilian University of Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), Munich,
Abstract
Tau aggregation, a defining feature of tauopathies, commonly appears as neuropil threads within neurites including axons. However, the affected neuronal populations and the spatial organization of axonal vulnerability remain poorly defined. Here, following identification of Tau accumulation in parvalbumin (PV) interneuron axons in primary tauopathy patients, we generated a P301S Tau model targeted to PV interneurons to track the structural integrity of their neurites and somas. We observed neuronal loss alongside axonal dystrophy, with focal swellings forming preferentially at axonal bifurcations. This spatial enrichment exceeded chance levels, and local axonal geometry predicted swelling localization. Longitudinal in vivo imaging revealed that bifurcation-associated swellings progressed to axonal severing. Analogous bifurcation-associated dystrophies were present in PV axons in human primary tauopathy tissue. These findings indicate that axonal branch geometry shapes the spatial pattern of Tau-induced neurodegeneration and identify PV axonal branch points as sites of pathology in mouse and human tauopathy.
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BibTeX
@misc{feyen2026axonal,
title = {{Axonal Branch Points of Parvalbumin Interneurons are Focal Sites of Tau-Induced Degeneration}},
author = {P. Feyen and Y. Zhang and T. Niedermeier and N. Landgraf and F. M. Bareyre and C. Vos and L. Paeger and J. Herms},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.17.751394},
url = {https://www.biorxiv.org/content/10.64898/2026.09.17.751394v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Axonal Branch Points of Parvalbumin Interneurons are Focal Sites of Tau-Induced Degeneration
AU - P. Feyen
AU - Y. Zhang
AU - T. Niedermeier
AU - N. Landgraf
AU - F. M. Bareyre
AU - C. Vos
AU - L. Paeger
AU - J. Herms
PY - 2026
DA - 2026/09/17
PB - bioRxiv
DO - 10.64898/2026.09.17.751394
UR - https://www.biorxiv.org/content/10.64898/2026.09.17.751394v1
AB - Tau aggregation, a defining feature of tauopathies, commonly appears as neuropil threads within neurites including axons. However, the affected neuronal populations and the spatial organization of axonal vulnerability remain poorly defined. Here, following identification of Tau accumulation in parvalbumin (PV) interneuron axons in primary tauopathy patients, we generated a P301S Tau model targeted to PV interneurons to track the structural integrity of their neurites and somas. We observed neuronal loss alongside axonal dystrophy, with focal swellings forming preferentially at axonal bifurcations. This spatial enrichment exceeded chance levels, and local axonal geometry predicted swelling localization. Longitudinal in vivo imaging revealed that bifurcation-associated swellings progressed to axonal severing. Analogous bifurcation-associated dystrophies were present in PV axons in human primary tauopathy tissue. These findings indicate that axonal branch geometry shapes the spatial pattern of Tau-induced neurodegeneration and identify PV axonal branch points as sites of pathology in mouse and human tauopathy.
ER -