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Alzheimer's & dementia : the journal of the Alzheimer's Association
Published

Choroidal-ventricular system abnormalities are linked to amyloid-β aggregation in Alzheimer's disease

Authors

Seyyed Ali Hosseini, Etienne Aumont, Nesrine Rahmouni, Marcel S Woo, Arthur C Macedo, Brandon Hall, Tevy Chan, Joseph Therriault, Lydia Trudel, Yansheng Zheng, Gleb Bezgin, Aurélie Lebrun, Jaime Fernandez Arias, Kely Quispialaya Socualaya, Cécile Tissot, Stijn Servaes, Yi-Ting Wang, Delphine Oliva-Lopez, Stuart Mitchell, Robert Hopewell, Chris Hung-Hsin Hsiao, Catherine Saleh, Jenna Stevenson, Firoza Lussier, Liyong Wu, Min Chu, Sanjeev Chawla, Vladimir Fonov, Gassan Massarweh, Yasser Iturria Medina, Jean-Paul Soucy, Karine Provost, David A Rudko, Thomas Karikari, Andréa Lessa Benedet, Nicholas J Ashton, Henrik Zetterberg, Maxime Montembeault, Paolo Vitali, Kaj Blennow, Serge Gauthier, D Louis Collins, Jesse Klostranec, Tharick A Pascoal, Pedro Rosa-Neto

Abstract

Alzheimers Dement. 2026 Feb;22(2):e71205. doi: 10.1002/alz.71205.

ABSTRACT

INTRODUCTION: Enlargement of the choroidal-ventricular system occurs in aging and Alzheimer's disease (AD), but emerging evidence links these abnormalities to amyloid beta (Aβ) aggregation. We tested this hypothesis by assessing associations between AD pathophysiology and choroidal-ventricular system measures across the AD continuum.

METHODS: Ventricular volume, choroid-plexus volume, and ventricular radioactivity after positron emission tomography (PET) tracer injections were analyzed in 385 Translational Biomarkers in Aging and Dementia (TRIAD) and 282 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants using linear models and partial correlations. A composite score combining these measures was also tested against established AD biomarkers.

RESULTS: With advancing AD stages, ventricular and choroid-plexus volumes increased while ventricular radioactivity declined. These measures were interrelated, and abnormalities appeared even in amyloid-negative elderly. Across cohorts, they correlated with amyloid- and tau-PET, cerebrospinal fluid (CSF) and plasma p-tau isoforms, glial fibrillary acidic protein (GFAP), and cognition. Voxel-wise analyses showed strong associations with cortical Aβ, mediating downstream tau effects.

DISCUSSION: Changes in the choroidal-ventricular system are mutually correlated and carry an additive-effect on cortical Aβ load.

PMID:41738400 | PMC:PMC12933412 | DOI:10.1002/alz.71205

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg