{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T06:52:08Z","timestamp":1775890328077,"version":"3.50.1"},"posted":{"date-parts":[[2025,1,28]]},"group-title":"Neuroscience","reference-count":85,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Plasma p-tau181 is a promising diagnostic marker of Alzheimer\u2019s disease (AD) pathology, reflecting amyloid accumulation, tau deposition, and downstream neurodegeneration that leads to cognitive impairment. However, the specificity of plasma p-tau181 to AD-related tau pathology remains unclear.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To assess whether plasma p-tau181 is differentially associated with volumetric changes in distinct hippocampal subfields and whether they mediate the relationship between plasma p-tau181 and cognition across the AD continuum.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>213 participants with normal cognition (N=57), mild cognitive impairment (N=109), and AD (N=47) from the Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI) were included for cross-sectional analyses of hippocampal subfield volume that was quantified using the Automatic Segmentation of Hippocampal Subfields (ASHS) software. A subset (n=89) was evaluated for one-year longitudinal changes in hippocampal subfield volume.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Higher plasma p-tau181 levels (pg\/mL) were associated with decreased volumes in the CA1 and dentate gyrus, bilaterally, and right entorhinal cortex (\n                    <jats:italic>ps<\/jats:italic>\n                    &lt; 0.05). Additionally, volumes of these subfields partially mediated the relationship between plasma p-tau181 and ADNI memory and executive function composite scores. Baseline plasma p-tau181, however, did not predict longitudinal atrophy of hippocampal subfields across diagnostic groups.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Plasma p-tau181 is differentially associated with hippocampal subfields that are closely related to both age- and AD-related neurodegeneration. Elevated plasma p-tau181 levels may reflect tau accumulation, and volumetric changes in CA1 and DG may mediate the detrimental effect of tau pathology on cognition.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.01.27.635113","type":"posted-content","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T10:00:17Z","timestamp":1738058417000},"source":"Crossref","is-referenced-by-count":1,"title":["Distinctive associations between plasma p-tau181 levels and hippocampal subfield volume across the Alzheimer\u2019s disease continuum"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2163-2164","authenticated-orcid":false,"given":"Adea","family":"Rich","sequence":"first","affiliation":[{"name":"Brown University School of Public Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1156-5704","authenticated-orcid":false,"given":"Hwamee","family":"Oh","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry and Human Behavior and Cognitive and Psychological Sciences, Brown University"},{"name":"Carney Institute for Brain Science, Brown University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041023084915000_2025.01.27.635113v1.1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0333-5"},{"key":"2026041023084915000_2025.01.27.635113v1.2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10040850"},{"key":"2026041023084915000_2025.01.27.635113v1.3","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1185-7"},{"key":"2026041023084915000_2025.01.27.635113v1.4","first-page":"e12131","article-title":"Concordance of CSF measures of Alzheimer\u2019s pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays","volume":"13","year":"2021","journal-title":"Alzheimers Dement Diagn Assess Dis Monit"},{"key":"2026041023084915000_2025.01.27.635113v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24517"},{"key":"2026041023084915000_2025.01.27.635113v1.6","doi-asserted-by":"crossref","unstructured":"Vemuri P , Jack CR . 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