Axonal dystrophies (AxDs) are swollen and tortuous neuronal processes that are associated with extracellular depositions of amyloid β (Aβ) and have been observed to contribute to synaptic alterations occurring in Alzheimer's disease. Understanding the temporal course of this axonal pathology is of high relevance to comprehend the progression of the disease over time. We performed a long-term in vivo study (up to 210 days of two-photon imaging) with two transgenic mouse models (dE9xGFP-M and APP-PS1xGFP-M). Interestingly, AxDs were formed only in a quarter of GFP-expressing axons near Aβ-plaques, which indicates a selective vulnerability. AxDs, especially those reaching larger sizes, had long lifetimes and appeared as highly plastic structures with large variations in size and shape and axonal sprouting over time. In the case of the APP-PS1 mouse only, the formation of new long axonal segments in dystrophic axons (re-growth phenomenon) was observed. Moreover, new AxDs could appear at the same point of the axon where a previous AxD had been located before disappearance (re-formation phenomenon). In addition, we observed that most AxDs were formed and developed during the imaging period, and numerous AxDs had already disappeared by the end of this time. This work is the first in vivo study analyzing quantitatively the high plasticity of the axonal pathology around Aβ plaques. We hypothesized that a therapeutically early prevention of Aβ plaque formation or their growth might halt disease progression and promote functional axon regeneration and the recovery of neural circuits.

Lidia Blazquez-Llorca

Susana Valero-Freitag

Eva Ferreira Rodrigues

Ángel Merchán-Pérez

J. Rodrigo Rodríguez

Mario M. Dorostkar

Javier DeFelipe

Jochen Herms

Acta Neuropathologica Communications

ACTA NEUROPATHOLOGICA COMMUNICATIONS (ANC) 在提交后的两个月内使用分子、细胞和形态学技术发表基于实验或人体组织的神经疾病机制的文章。

The journal Acta neuropathologica communications (ANC) aims to publish articles on the mechanisms of neurological diseases based on experimental or human tissue within two months of submission, utilizing molecular, cellular, and morphological techniques.

《Acta neuropathologica communications》（ANC）期刊致力于在提交后的两个月内，利用分子、细胞和形态学技术，发表关于神经疾病机制的研究文章，这些研究基于实验或人体组织。

Acta neuropathologica communications

High plasticity of axonal pathology in Alzheimer’s disease mouse models

This work is the first in vivo study analyzing quantitatively the high plasticity of the axonal pathology around Aβ plaques and hypothesized that a therapeutically early prevention of Aβ plaque formation or their growth might halt disease progression and promote functional axon regeneration and the recovery of neural circuits.

Category	Quartile
医学	2
医学, 神经科学	2

High plasticity of axonal pathology in Alzheimer’s disease mouse models

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