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This review integrates recent findings from epidemiological studies, clinical data, and mechanistic research to provide a comprehensive overview of HHcy's contribution to neurovascular dysfunction. We examine how nutritional deficits, aging, genetic polymorphisms\u2014such as in the methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta\u2010synthase (CBS) genes\u2014pharmacological agents, and comorbid conditions shape homocysteine homeostasis and susceptibility to pathology. Emphasis is placed on molecular pathways, including oxidative and nitrative stress, inflammasome activation, autophagy, and epigenetic modulation, which link HHcy to cognitive decline, memory impairment, endothelial dysfunction, and increased disease burden in neurodegenerative disorders. By consolidating multidisciplinary evidence, we position HHcy as a pivotal but under\u2010recognized target for intervention in neurochemical and vascular health.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70327-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70327","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T13:52:23Z","timestamp":1766411543000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Uncovering Hyperhomocysteinemia: Global Risk Patterns and Molecular Disruption in Brain and Vascular Health"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2827-8349","authenticated-orcid":false,"given":"Osmar Vieira","family":"Ramires J\u00fanior","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Bioci\u00eancias Universidade Federal de Ci\u00eancias da Sa\u00fade de Porto Alegre (UFCSPA)  Porto Alegre Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3412-1400","authenticated-orcid":false,"given":"Gustavo Ricardo Krupp","family":"Prauchner","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica, Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade (ICBS) Universidade Federal do Rio Grande do Sul (UFRGS)  Porto Alegre Rio Grande do Sul Brazil"},{"name":"Laborat\u00f3rio de Neuroprote\u00e7\u00e3o e Doen\u00e7as Neurometab\u00f3licas, Departamento de Bioqu\u00edmica ICBS, UFRGS  Porto Alegre Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1220-8066","authenticated-orcid":false,"given":"Alessandra Schmitt","family":"Rieder","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica, Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade (ICBS) Universidade Federal do Rio Grande do Sul (UFRGS)  Porto Alegre Rio Grande do Sul Brazil"},{"name":"Laborat\u00f3rio de Neuroprote\u00e7\u00e3o e Doen\u00e7as Neurometab\u00f3licas, Departamento de Bioqu\u00edmica ICBS, UFRGS  Porto Alegre Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3228-5165","authenticated-orcid":false,"given":"Ana Karla Oliveira","family":"Leite","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Cogni\u00e7\u00e3o e Neurobiologia da Mem\u00f3ria, Instituto Do C\u00e9rebro Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul (PUCRS)  Porto Alegre Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9789-3092","authenticated-orcid":false,"given":"Clarissa Penha","family":"Farias","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Cogni\u00e7\u00e3o e Neurobiologia da Mem\u00f3ria, Instituto Do C\u00e9rebro Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul (PUCRS)  Porto Alegre Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8769-1147","authenticated-orcid":false,"given":"Angela T. 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