Exploring the spatial covariance of cerebral vascular density and amyloid burden in Alzheimer's disease
Lucia Argenti, Alessio Cirone, Federico Massa, Elena Sentieri, Mattia Losa, Luigi Lorenzini, Sara Garbarino, Luca Sofia, Stefano Raffa, Matteo Bauckneht, Gianmario Sambuceti, Wendy Kreshpa, Giulia Bozzo, Giulia Tomassini, Francesca De Cesari, Virginia Pelagotti, Martina Pulze, Lorenzo Gualco, Mehrnaz Hamedani, Chiara Razzetta, Andrea Brugnolo, Nicola Girtler, Stefano Caneva, Pietro Mattioli, Silvia Morbelli, Shahzad Ali, Michele Piana, Carlo Serrati, Antonio Uccelli, Andrea Chincarini, Dario Arnaldi, Luca Roccatagliata, Fabio Bandini, Beatrice Orso, Matteo PardiniAbstract
INTRODUCTION
Regional patterns of amyloid beta (Aβ) deposition in Alzheimer's disease (AD) may be influenced by cerebrovascular architecture. We examined the relationship between normative arterial and venous density maps and cortical Aβ burden.
METHODS
Seventy‐four amyloid‐positive AD patients underwent amyloid positron emission tomography (PET) and magnetic resonance imaging. Regional Aβ uptake was quantified; spatial associations with normative arterial (time‐of‐flight magnetic resonance angiography) and venous (susceptibility‐weighted imaging) density maps were assessed using correlation analyses and partial least squares (PLS) regression, controlling for early‐frame PET as a proxy for perfusion.
RESULTS
Higher arterial density was associated with lower Aβ uptake ( r = −0.68, p < 0.001), independent of venous density and perfusion. PLS explained 71% of regional variance, highlighting temporo‐limbic regions. Subject‐level analyses showed heterogeneous vascular–amyloid coupling, related to education and global Aβ burden.
DISCUSSION
Arterial architecture may contribute to regional amyloid vulnerability through vascular clearance mechanisms.