{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T15:14:09Z","timestamp":1790954049956,"version":"4.1.0"},"reference-count":101,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain small vessel disease (SVD) refers to a variety of structural and functional changes affecting small arteries and micro vessels, and manifesting as white matter changes, microbleeds and lacunar infarcts. Growing evidence indicates that SVD might play a significant role in the neurobiology of central nervous system (CNS) neurodegenerative disorders, namely Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD), and neuroinflammatory diseases, such as multiple sclerosis (MS). These disorders share different pathophysiological pathways and molecular mechanisms (i.e., protein misfolding, derangement of cellular clearance systems, mitochondrial impairment and immune system activation) having neurodegeneration as biological outcome. In these diseases, the actual contribution of SVD to the clinical picture, and its impact on response to pharmacological treatments, is not known yet. Due to the high frequency of SVD in adult-aged patients, it is important to address this issue. In this review, we report preclinical and clinical data on the impact of SVD in AD, PD and MS, with the main aim of clarifying the predictability of SVD on clinical manifestations and treatment response.<\/jats:p>","DOI":"10.3390\/ijms22094958","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T10:06:12Z","timestamp":1620381972000},"page":"4958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["The Contribution of Small Vessel Disease to Neurodegeneration: Focus on Alzheimer\u2019s Disease, Parkinson\u2019s Disease and Multiple Sclerosis"],"prefix":"10.3390","volume":"22","author":[{"given":"Federico","family":"Paolini Paoletti","sequence":"first","affiliation":[{"name":"Section of Neurology, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Simoni","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5722-3967","authenticated-orcid":false,"given":"Lucilla","family":"Parnetti","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3967-8954","authenticated-orcid":false,"given":"Lorenzo","family":"Gaetani","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/S1474-4422(19)30079-1","article-title":"Small vessel disease: Mechanisms and clinical implications","volume":"18","author":"Wardlaw","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/S1474-4422(13)70124-8","article-title":"Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration","volume":"12","author":"Wardlaw","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1177\/1747493015607485","article-title":"The concept of sporadic cerebral small vessel disease: A road map on key definitions and current concepts","volume":"11","author":"Charidimou","year":"2016","journal-title":"Int. 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