Peripheral Administration of isoD7-Aβ Exacerbates Motor Deficits and Tau Pathology in P301S Mice.

Animal / preclinicalFrontiers in bioscience (Landmark edition)· Jul 2026

Peripheral Administration of isoD7-Aβ Exacerbates Motor Deficits and Tau Pathology in P301S Mice.

Yulia Stepenko, Olesya Shcheblykina, Nikita Zhunusov … Mikhail Korokin

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NeuropathologyAnimal / preclinical

Peripheral amyloid-β exposure was linked to earlier motor impairment onset in mice.

Peripheral Administration of isoD7-Aβ Exacerbates Motor Deficits and Tau Pathology in P301S Mice.

Yulia Stepenko … Mikhail Korokin

Frontiers in bioscience (Landmark edition) · Jul 2026

Background

Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to dementia, disability, and premature death.

Purpose

To evaluate the effect of double peripheral (retro-orbital) administration of the Aβ isoform D7 on the behavioral phenotype, morphological signs of tau pathology, and the expression of genes related to Akt/GSK-3β-associated signaling, neuroinflammation, and apoptosis in the brains of P301S transgenic mice.

Methods

The study included 12-week-old male P301S transgenic mice (Tg(Thy1-MAPT*P301S)2541Godt) (n = 20, biological duplication) and wild-type C57Black6/J mice (n = 10).

n = 20,

week 16

Results

week 16

amyloid-exposed mice showed motor decline earlier than mice without exposure

n = 20,

More results

Two peripheral administrations of isoD7-Aβ were not associated with further deterioration of performance in the "open field" and "novel object recognition" tests compared to the control P301S group, which likely reflects the already established deficit characteristic of this transgenic line.

More results

Immunohistochemical analysis revealed an increase in AT-8-positive staining in the brainstem, whereas no statistically significant differences were found between groups in the frontal cortex.

Histological analysis did not reveal amyloid plaques in the entorhinal cortex and hippocampus of P301S+Aβ mice and control P301S mice.

“

Conclusion

Two peripheral administrations of isoD7-Aβ to P301S mice were associated with earlier development of motor impairments, increased tau protein phosphorylation, and changes in gene expression consistent with a disrupted Akt/GSK-3β-associated signaling pathway.

Peripheral Administration of isoD7-Aβ Exacerbates Motor Deficits and Tau Pathology in P301S Mice.

Peripheral Administration of isoD7-Aβ Exacerbates Motor Deficits and Tau Pathology in P301S Mice.

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