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However, longitudinal positron emission tomography (PET) studies examining PVS as a mechanism underlying Alzheimer's disease (AD) pathophysiological progression are lacking. Our overall objective was to investigate the associations of baseline PVS burden with white matter hyperintensity (WMH) volume, amyloid\u2010PET, and tau\u2010PET, both cross\u2010sectionally and longitudinally.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We examined 2,229 participants across the aging\u2010AD spectrum from the Mayo Clinic Study of Aging (MCSA) and the Mayo Alzheimer's Disease Research Center (ADRC) (mean age\u2009=\u200968.59\u2009\u00b1\u200912.70 and 48.94% women). PVS and WMH were quantified using a novel in\u2010house algorithm. Amyloid on [\n                      <jats:sup>11<\/jats:sup>\n                      C]Pittsburgh Compound B (PiB)\u2010PET and tau on AV1451\u2010PET were measured. Cross\u2010sectional regional and global associations were examined using canonical correlation analysis (CCA). Longitudinal associations were examined using age\u2010 and sex\u2010adjusted linear mixed effect (LME) models with natural splines and subject\u2010wise 10\u2010fold cross\u2010validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>Three distinct associations were observed: (1) PVS in the basal ganglia (PVS\u2010BG) was associated with greater WMH volume both cross\u2010sectionally and longitudinally; (2) PVS\u2010BG covaried with higher PiB standardized uptake value ratio (SUVR) cross\u2010sectionally, with longitudinal trajectory associations limited to amyloid\u2010negative individuals; (3) PVS in the centrum semiovale (PVS\u2010CSO) was not associated with amyloid or tau, but was associated with occipital WMH, a pattern characteristic of CAA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Findings lend support for PVS\u2010BG as an early indicator of small vessel dysfunction and WMH pathogenesis. Individuals with higher PVS\u2010BG burden exhibited higher WMH burden and faster WMH progression, suggesting that PVS\u2010BG may identify individuals at increased risk of progressive SVD. Evidence linking PVS to downstream AD biomarker progression was weaker. Findings support the relevance of PVS\u2010CSO to CAA, suggesting that they may reflect changes occurring early in the disease process. ANN NEUROL 2026;100:695\u2013708<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78299","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T03:36:00Z","timestamp":1784345760000},"page":"695-708","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Perivascular Spaces as Determinants of Amyloid, Tau, and Vascular Biomarker Progression"],"prefix":"10.1002","volume":"100","author":[{"given":"Audrey","family":"Low","sequence":"first","affiliation":[{"name":"Department of Radiology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Gunter","sequence":"additional","affiliation":[{"name":"Department of Radiology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health 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