Association of Choroid Plexus Volume With Serum Biomarkers, Clinical Features, and Disease Severity in Patients With Frontotemporal Lobar Degeneration Spectrum

Background and objectives: Choroid plexus (ChP) is emerging as a key brain structure in the pathophysiology of neurodegenerative disorders. In this observational study we investigated ChP volume in a large cohort of frontotemporal lobar degeneration (FTLD) spectrum patients to explore a possible link between ChP volume and other disease-specific biomarkers.

Methods: Participants included patients meeting clinical criteria for a probable syndrome in the FTLD spectrum. Structural brain MRI imaging, serum neurofilament light (NfL) and serum phosphorylated-Tau₁₈₁ (p-Tau₁₈₁), cognitive and behavioral data were collected. MRI ChP volumes were obtained from an ad-hoc segmentation model based on a Gaussian Mixture Models (GMM) algorithm.

Results: Three-hundred and sixteen patients within FTLD spectrum were included in this study, specifically 135 patients diagnosed with behavioral variant frontotemporal dementia (bvFTD), 75 primary progressive aphasia (PPA), 46 progressive supranuclear palsy (PSP), 60 corticobasal syndrome (CBS). In addition, 82 age-matched healthy subjects were recruited as controls (HC). ChP volume was significantly larger in FTLD patients compared with HC, across the clinical subtype. Moreover, we found a significant difference in ChP volume between HC and patients stratified for disease-severity based on CDRplus NACC FTLD, including patients at very early stage of the disease. Interestingly, ChP volume correlated with serum NfL, cognitive/behavioural deficits, as well as with patterns of cortical atrophy. Finally, ChP volume seemed to discriminate HC from FTLD patients better than other previously identified brain structure volumes.

Discussion: Considering the clinical, pathological, and genetic heterogeneity of the disease, ChP could represent a potential biomarker across the FTLD spectrum, especially at the early stage of disease. Further longitudinal studies are needed to establish its role in disease onset and progression.

Classification of Evidence: This study provides Class III evidence that choroid plexus volume, as measured on MRI scan, can assist in differentiating patients with FTLD from healthy controls, and in characterizing disease severity.