{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:08:30Z","timestamp":1778875710423,"version":"3.51.4"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":99,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Finanziato dall\u2019Unione europea\u2014Next Generation EU\u2014PNRR M6C2\u2014Investimento 2.1 Valorizzazione e potenziamento della ricerca biomedica del SSN","award":["PNRR-MAD-2022-12376667"],"award-info":[{"award-number":["PNRR-MAD-2022-12376667"]}]},{"name":"Finanziato dall\u2019Unione europea\u2014Next Generation EU\u2014PNRR M6C2\u2014Investimento 2.1 Valorizzazione e potenziamento della ricerca biomedica del SSN","award":["C53C22001550006"],"award-info":[{"award-number":["C53C22001550006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2013like pathology in human and rodent brains. This study employed a murine model showing an Alzheimer's disease\u2013related 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\u2013like pathology. Mice were subjected to two (2\u00d7TS) or seven thermal stress (7\u00d7TS) 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\u00d7TS HSV-1 mice showed a reduced preference index in Novel Object Recognition compared to mice receiving mock infection (i.e. vehicle inoculum), whereas 7\u00d7TS 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\u00d7TS HSV-1 mice compared to controls, with negative correlations between total coherence and grip strength. Increased spine density in the frontal cortex of 2\u00d7TS 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.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag128","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T11:44:15Z","timestamp":1775735055000},"source":"Crossref","is-referenced-by-count":0,"title":["EEG\u2013motor correlation as early Alzheimer\u2019s disease index in herpes simplex virus type-1\u2013infected mice"],"prefix":"10.1093","volume":"8","author":[{"given":"Chiara","family":"D\u2019Amelio","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore , Rome 00168 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Feroleto","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore , Rome 00168 ,","place":["Italy"]},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome 00168 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Caligiuri","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore , Rome 00168 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenica Donatella","family":"Li Puma","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore , Rome 00168 ,","place":["Italy"]},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome 00168 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2219-6097","authenticated-orcid":false,"given":"Giovanna","family":"De Chiara","sequence":"additional","affiliation":[{"name":"Institute of Translational Pharmacology, Natl. Res. Council , Rome 00133 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Paoletti","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome 00168 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camilla","family":"Codazzi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore , Rome 00168 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"D\u2019Alelio","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome 00168 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Miraglia","sequence":"additional","affiliation":[{"name":"Brain Connectivity Laboratory, Department of Neuroscience and Neurorehabilitation, IRCCS San Raffaele , Rome 00166 ,","place":["Italy"]},{"name":"Department of Theoretical and Applied Sciences, eCampus University , Novedrate, Como 22060 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Pappalettera","sequence":"additional","affiliation":[{"name":"Brain Connectivity Laboratory, Department of Neuroscience and Neurorehabilitation, IRCCS San Raffaele , Rome 00166 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Nucci","sequence":"additional","affiliation":[{"name":"Brain Connectivity Laboratory, Department of Neuroscience and Neurorehabilitation, IRCCS San Raffaele , Rome 00166 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Frasca","sequence":"additional","affiliation":[{"name":"Brain Connectivity Laboratory, Department of Neuroscience and Neurorehabilitation, IRCCS San Raffaele , Rome 00166 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Ventura","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliero Universitaria di Sassari , Sassari 07100 ,","place":["Italy"]},{"name":"Department of Biomedical Sciences, University of Sassari , Sassari 07100 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Manca","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari , Sassari 07100 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Morrone","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari , Sassari 07100 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Leone","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore , Rome 00168 ,","place":["Italy"]},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome 00168 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8235-6091","authenticated-orcid":false,"given":"Franca","family":"Deriu","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliero Universitaria di Sassari , Sassari 07100 ,","place":["Italy"]},{"name":"Department of Biomedical Sciences, University of Sassari , Sassari 07100 ,","place":["Italy"]},{"name":"Unit of Endocrinology, Nutrition, and Metabolic Disorders, AOUSS , Sassari 07100 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1878-0159","authenticated-orcid":false,"given":"Marta","family":"Morotti","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario A. 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