{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:10:17Z","timestamp":1791897017713,"version":"4.3.4"},"reference-count":90,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Neurodegenerative diseases (NDs) are increasingly considered neurometabolic disorders driven by early mitochondrial dysfunction, neuroinflammation, and synaptic alterations that precede clinical symptoms. This review summarises pre-clinical and experimental evidence suggesting that intermittent fasting (IF) may influence these early pathogenic processes by promoting metabolic switching, enhancing autophagy and mitochondrial quality control, and modulating neuroimmune pathways. We discuss recent advances in biomarker research supporting the early detection of neurodegenerative changes, including ultrasensitive analytical platforms that can identify neuronal, glial, and synaptic injury during preclinical stages. By integrating these biomarker developments with findings from human and experimental intermittent fasting studies, we highlight how high-sensitivity assays provide quantifiable insights into the neurometabolic effects of fasting. Furthermore, we discuss how precision nutrition strategies incorporating multimarker panels, phenotypic and epigenetic signatures, and longitudinal multi-omics profiling may facilitate personalised intermittent fasting protocols and improve monitoring of biological responses. Overall, these findings underscore the relevance of a clinical biochemistry perspective integrating advanced biomarker technologies to evaluate the neurometabolic effects of intermittent fasting as a potential early neuroprotective strategy for individuals at risk of neurodegeneration.<\/jats:p>","DOI":"10.3390\/cimb48040358","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T12:11:44Z","timestamp":1774872704000},"page":"358","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring Early Neurodegeneration Through Fasting-Induced Metabolic Signatures and High-Sensitivity Biomarkers"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9886-2385","authenticated-orcid":false,"given":"Francesco","family":"Cacciabaudo","sequence":"first","affiliation":[{"name":"Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Agnello","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"},{"name":"Department of Laboratory Medicine, University Hospital Paolo Giaccone, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina Maria","family":"Gambino","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"},{"name":"Department of Laboratory Medicine, University Hospital Paolo Giaccone, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3565-9529","authenticated-orcid":false,"given":"Giulia","family":"Accardi","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Masucci","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Tamburello","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Vassallo","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6120-9041","authenticated-orcid":false,"given":"Marcello","family":"Ciaccio","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"},{"name":"Department of Laboratory Medicine, University Hospital Paolo Giaccone, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"ref_1","unstructured":"The GBD 2021 Nervous System Disorders Collaborators (2024). 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