{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:01:08Z","timestamp":1790402468636,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Vascular dysfunction is increasingly recognized as a key contributor to Alzheimer's disease (AD). This study explored cerebrovascular reactivity (CVR), measured by the breath\u2010holding index (BHI) via Transcranial Doppler (TCD), in relation to plasma AD biomarkers, metabolic dysfunction, cardiovascular burden, and apolipoprotein E (APOE) genotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We enrolled 64 patients with cerebrospinal fluid (CSF)\u2010confirmed AD (30 APOE \u03b53, 34 APOE \u03b54) and 28 age\u2010matched healthy controls in a cross\u2010sectional blinded study. All participants underwent TCD to assess middle cerebral artery flow velocity and BHI. AD patients were further evaluated for insulin resistance (TyG index), magnetic resonance imaging markers of small vessel disease (SVD), and plasma biomarkers (phosphorylated tau 181 [p\u2010tau181], amyloid beta [A\u03b2]42\/A\u03b240 ratio \u2013 AmyR). Multivariate regressions examined associations between BHI and AD\u2010related parameters, stratified by APOE genotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      BHI was significantly reduced in both AD groups compared to controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001), with no difference between \u03b53 and \u03b54 carriers. In \u03b53 patients, lower BHI was independently associated with higher plasma p\u2010tau181. In the MRI subgroup analysis, \u03b53 patients showed a negative correlation between BHI and both TyG and mCSVD while showing a positive correlation with AmyR. None of these associations were observed in \u03b54 carriers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our findings indicate that CVR impairment is present across AD genotypes but more strongly linked to AD pathology and vascular\u2010metabolic dysfunction in APOE \u03b53 carriers. CVR may represent a non\u2010invasive biomarker of early vascular contributions to cognitive decline in AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70250","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:36:36Z","timestamp":1782902196000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cerebrovascular reactivity and plasma p\u2010tau181 in Alzheimer's disease: Insights into APOE\u2010related vascular phenotypes"],"prefix":"10.1002","volume":"12","author":[{"given":"Martina Gaia","family":"Di Donna","sequence":"first","affiliation":[{"name":"Memory Clinic and Neurodegenerative Dementia Research Unit Policlinico Tor Vergata University of Rome \u201cTor Vergata\u201d  Rome Italy"},{"name":"Stroke Unit, Hospital F. 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