EEG-motor correlation as early Alzheimer's disease index in herpes simplex virus type-1-infected mice.

Overview

1. Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome 00168, Italy
2. Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
3. Institute of Translational Pharmacology, Natl. Res. Council, Rome 00133, Italy
4. Brain Connectivity Laboratory, Department of Neuroscience and Neurorehabilitation, IRCCS San Raffaele, Rome 00166, Italy
5. Department of Theoretical and Applied Sciences, eCampus University, Novedrate, Como 22060, Italy
6. Azienda Ospedaliero Universitaria di Sassari, Sassari 07100, Italy
7. Department of Biomedical Sciences, University of Sassari, Sassari 07100, Italy
8. Unit of Endocrinology, Nutrition, and Metabolic Disorders, AOUSS, Sassari 07100, Italy

Abstract

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive decline and memory impairment. Early treatment requires reliable tests to identify the initial manifestations for developing treatments that modify disease progression. Neuroinflammation has been implicated as a key driver of the onset and progression of Alzheimer's disease. Herpes simplex virus type-1 (HSV-1), a neurotropic virus that establishes latency within the central nervous system, has been associated with increased proinflammatory cytokines, cognitive impairment and Alzheimer's disease–like pathology in human and rodent brains. This study employed a murine model showing an Alzheimer's disease–related phenotype, induced by HSV-1 infection and recurrent reactivation through thermal stress, to investigate previously unexplored motor function impairments and their correlation with EEG changes predictive of Alzheimer's disease–like pathology. Mice were subjected to two (2×TS) or seven thermal stress (7×TS) HSV-1 reactivations to reproduce mild and severe cognitive impairments, respectively, and were tested for recognition memory using the Novel Object Recognition test and for spatial memory using the Y-maze test. Motor performance was assessed using grip strength and grid walking tests. Local field potential recordings, immunohistochemical, morphological and molecular analyses were performed to characterize the effects of HSV-1 on neural circuits. 2×TS HSV-1 mice showed a reduced preference index in Novel Object Recognition compared to mice receiving mock infection (i.e. vehicle inoculum), whereas 7×TS HSV-1 mice displayed severe cognitive decline across the different memory domains. Motor function was preserved after the second thermal stress but was impaired after the seventh thermal stress, with reduced forelimb force and increased foot faults starting from the fourth reactivation. Following the seventh reactivation, HSV-1 mice showed astrogliosis and phosphorylated Tau accumulation. In vivo, electrophysiological recordings revealed increased functional connectivity across frequency bands in 2×TS HSV-1 mice compared to controls, with negative correlations between total coherence and grip strength. Increased spine density in the frontal cortex of 2×TS HSV-1 mice supports early neuronal network alterations. From a translational perspective, we preliminarily evaluated comparable motor indices in healthy human participants, in patients with mild cognitive impairment, and in patients with Alzheimer's disease. As expected, both grip strength and dynamic balance were lower in patients with Alzheimer's disease compared to healthy and mild cognitive impairment subjects. Notably, grip strength was significantly reduced in mild cognitive impairment subjects, who displayed early motor impairment. Our findings highlight the potential of EEG-based biomarkers for early Alzheimer's disease detection and suggest motor indices as novel prognostic markers.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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• zenodo:19912254, at Zenodo; found in “Data availability”

Data availability

The data supporting the findings of this study are available in the article and at DOI https://doi.org/10.5281/zenodo.19912254. Anonymised data may be shared by the senior authors upon reasonable request. Data sharing may be subject to restrictions according to consent and data protection legislation. MATLAB scripts used in the data analysis employed standard functions and packages that are freely available; no new package or function was generated for this study.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 21 authors, 5 keywords, 37 references.

Cite

This paper

D’Amelio, C., Feroleto, C., Caligiuri, C., Li Puma, D. D., De Chiara, G., Paoletti, I., Codazzi, C., D’Alelio, F., Miraglia, F., Pappalettera, C., Nucci, L., Frasca, F., Ventura, L., Manca, A., Morrone, M., Leone, L., Deriu, F., Morotti, M., Grassi, C., . . . Podda, M. V. (2026). EEG-motor correlation as early Alzheimer's disease index in herpes simplex virus type-1-infected mice. Brain communications, 8(3), fcag128. https://doi.org/10.1093/braincomms/fcag128

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