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However, impaired astrocytic support may also contribute. The locus coeruleus (LC), which degenerates early in aging and Alzheimer's disease, provides widespread noradrenergic projections that regulate astrocytic metabolism via \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010adrenergic signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      In a healthy aging cohort (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a0106), we quantified LC volume, WMHs, and voxel\u2010wise (q\u2010WMHs). Associations were tested, controlling for age, cardiovascular risk, and other subcortical nuclei. Spatial partial least squares regression related q\u2010WMH patterns to LC volume, age, and cortical adrenergic receptor expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      LC volume was independently associated with WMH burden and mediated age\u2010related WMH increases. A latent q\u2010WMH pattern aligned with cortical \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010adrenergic receptor expression and mediated its association with WMH burden.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      LC degeneration may contribute to regional WMH vulnerability through noradrenergic mechanisms consistent with astrocytic \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010adrenergic signaling, highlighting a potential nonvascular pathway influencing white matter integrity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71583","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T02:51:37Z","timestamp":1781751097000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["White matter hyperintensities are associated with locus coeruleus atrophy and astrocytic \u03b2\n                    <sub>2<\/sub>\n                    \u2010adrenergic receptor expression"],"prefix":"10.1002","volume":"22","author":[{"given":"Victor","family":"Vidal","sequence":"first","affiliation":[{"name":"Brain and Mind Centre The University of Sydney  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Far\u00edas","sequence":"additional","affiliation":[{"name":"Departamento de Neurociencia Facultad de Medicina Universidad de Chile  Santiago Chile"},{"name":"Hospital Cl\u00ednico de la Universidad de Chile  Santiago 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