Choroid plexus volume in Alzheimer's disease: A systematic review and meta-analysis

Abstract

Background Alzheimer's disease (AD) is marked by amyloid-beta and tau accumulation, processes increasingly linked to impaired protein clearance and neuroinflammation. The choroid plexus (CP), which regulates cerebrospinal fluid (CSF) production and immune signaling, may contribute to these mechanisms. This review aimed to evaluate alterations in CP volume (CPV) in AD and their clinical significance. Methods PubMed, Embase, Scopus, and Web of Science were searched up to March 2025. Eligible MRI-based studies comparing CPV between AD patients and healthy controls (HCs), as well as investigations examining associations of CPV with demographic, cognitive, structural, and pathological variables, were included. Random-effects models estimated pooled effect sizes, while narrative synthesis explored associations with clinical and pathological features. Results Sixteen studies (2004 AD; 883 HCs) met inclusion criteria. Pooled findings demonstrated significantly larger CPV in AD relative to HCs (SMD = 1.05, 95 CI: 0.67 to 1.43; p < 0.01). Narrative review indicated consistent links between CP enlargement and worse cognition, hippocampal and cortical atrophy, ventricular expansion, and increased amyloid and tau deposition. CP changes were also associated with impaired glymphatic clearance and systemic inflammation. Notably, enlargement was observed in mild cognitive impairment, suggesting early involvement in the disease course. Conclusions CP enlargement may represent a neuroimaging feature of AD, reflecting the interplay between impaired clearance mechanisms and neuroinflammatory processes. Given its visibility on routine MRI, CPV may hold considerable potential as an imaging marker for disease stratification and longitudinal monitoring of AD.