{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:34:21Z","timestamp":1787312061639,"version":"build-2736575974"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      The apolipoprotein E\n                      <jats:italic>(APOE)<\/jats:italic>\n                      \u03b54 allele is the main genetic risk factor for dementia and Alzheimer's disease (AD), but the underlying mechanism for the increased risk is not well understood. Cerebral small vessel disease (SVD) is prevalent among patients with cognitive impairment and is thought to play an important role in the pathophysiology of dementia. We aimed to investigate the association between the\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b5 genotype and magnetic resonance imaging (MRI) markers of SVD in a memory clinic population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>\n                      This is a cross-sectional study with a total of 520 patients undergoing dementia investigation, including an MRI brain scan and\n                      <jats:italic>APOE<\/jats:italic>\n                      genotyping in all patients enrolled, and cerebrospinal fluid (CSF) analysis for routine AD biomarkers in 399 patients. MR images were assessed for markers of SVD: cerebral microbleeds (CMBs), cortical superficial siderosis, intracerebral hemorrhage, white matter hyperintensities, lacunar infarcts, and enlarged perivascular spaces.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Apolipoprotein E carriers with AD had a higher number of CMBs when looking at all brain regions and lobar brain regions (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). A lower number of CMBs were seen in\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b52 (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05), \u03b53 and \u03b53\/3 carriers (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001) when looking at all brain regions. A higher number of CMBs in deep and infratentorial regions were seen in\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b52 and \u03b53 (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05). In\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\/4 carriers, CMBs, cortical superficial siderosis, white matter hyperintensities, and enlarged perivascular spaces were associated with lower levels of CSF amyloid \u03b2 (A\u03b2) 42 in the whole cohort, and in individuals with AD and mild cognitive impairment (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Apolipoprotein E \u03b54 is associated with MRI markers of SVD related to amyloid pathology, specifically CMBs and A\u03b242 plaque formation in the brain, as reflected by decreased CSF A\u03b242 levels, whereas\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b53 and \u03b52 are associated with the markers of hypertensive arteriopathy, as reflected by the association with CMBs in deep and infratentorial brain regions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2022.897674","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T05:02:41Z","timestamp":1657688561000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["MRI Markers of Small Vessel Disease and the APOE Allele in Cognitive Impairment"],"prefix":"10.3389","volume":"14","author":[{"given":"Mana","family":"Shams","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Shams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Martola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Cavallin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Granberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Kaijser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Wintermark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Westman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Aspelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kristoffersen Wiberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars-Olof","family":"Wahlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"551","DOI":"10.2214\/ajr.151.3.551","article-title":"Brain MR: pathologic correlation with gross and histopathology. 1. 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