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

Martina Assogna; Enrico Premi; Stefano Gazzina; Alberto Benussi; Nicholas J Ashton; Henrik Zetterberg; Kaj Blennow; Roberto Gasparotti; Alessandro Padovani; Ehsan Tadayon; Sara Romanella; Giulia Sprugnoli; Alvaro Pascual-Leone; Francesco Di Lorenzo; Giacomo Koch; Barbara Borroni; Emiliano Santarnecchi

doi:10.1212/WNL.0000000000207600

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

Neurology. 2023 Sep 19;101(12):e1218-e1230. doi: 10.1212/WNL.0000000000207600. Epub 2023 Jul 27.

Authors

Martina Assogna¹, Enrico Premi¹, Stefano Gazzina¹, Alberto Benussi¹, Nicholas J Ashton¹, Henrik Zetterberg¹, Kaj Blennow¹, Roberto Gasparotti¹, Alessandro Padovani¹, Ehsan Tadayon¹, Sara Romanella¹, Giulia Sprugnoli¹, Alvaro Pascual-Leone¹, Francesco Di Lorenzo¹, Giacomo Koch¹, Barbara Borroni¹, Emiliano Santarnecchi²

Affiliations

¹ From the Precision Neuroscience & Neuromodulation Program (M.A., S.R., G.S., E.S.), Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Non-Invasive Brain Stimulation Unit (M.A., F.D.L., G.K.), Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS; Memory Clinic (M.A.), Department of Systems Medicine, University of Tor Vergata, Rome; Neurology Unit (E.P., S.G., A.B., A.P., B.B.), Department of Clinical and Experimental Sciences, University of Brescia, Italy; Institute of Neuroscience and Physiology (N.J.A.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Mӧlndal, Sweden; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), United Kingdom; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (H.Z.), London, United Kingdom; Hong Kong Center for Neurodegenerative Diseases (H.Z.), Clear Water Bay, Hong Kong, China; Neuroradiology Unit (R.G.), University of Brescia, Italy; Berenson-Allen Center for Noninvasive Brain Stimulation (E.T.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Department of Medicine (G.S.), Surgery and Neuroscience, Siena Brain Investigation & Neuromodulation Laboratory, University of Siena, Siena, Italy; Hinda and Arthur Marcus Institute for Aging Research at Hebrew SeniorLife (A.P.-L.); Department of Neurology (A.P.-L.), Harvard MedicalSchool, Boston, MA, USA; and Department of Neuroscience and Rehabilitation (G.K.), University of Ferrara, Italy.
² From the Precision Neuroscience & Neuromodulation Program (M.A., S.R., G.S., E.S.), Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Non-Invasive Brain Stimulation Unit (M.A., F.D.L., G.K.), Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS; Memory Clinic (M.A.), Department of Systems Medicine, University of Tor Vergata, Rome; Neurology Unit (E.P., S.G., A.B., A.P., B.B.), Department of Clinical and Experimental Sciences, University of Brescia, Italy; Institute of Neuroscience and Physiology (N.J.A.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Mӧlndal, Sweden; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), United Kingdom; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (H.Z.), London, United Kingdom; Hong Kong Center for Neurodegenerative Diseases (H.Z.), Clear Water Bay, Hong Kong, China; Neuroradiology Unit (R.G.), University of Brescia, Italy; Berenson-Allen Center for Noninvasive Brain Stimulation (E.T.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Department of Medicine (G.S.), Surgery and Neuroscience, Siena Brain Investigation & Neuromodulation Laboratory, University of Siena, Siena, Italy; Hinda and Arthur Marcus Institute for Aging Research at Hebrew SeniorLife (A.P.-L.); Department of Neurology (A.P.-L.), Harvard MedicalSchool, Boston, MA, USA; and Department of Neuroscience and Rehabilitation (G.K.), University of Ferrara, Italy. esantarnecchi@mgh.harvard.edu.

PMID: 37500561
PMCID: PMC10516270 (available on 2024-09-19)
DOI: 10.1212/WNL.0000000000207600

Abstract

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 patients with frontotemporal lobar degeneration (FTLD) spectrum 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), serum phosphorylated-Tau₁₈₁ (p-Tau₁₈₁), and cognitive and behavioral data were collected. MRI ChP volumes were obtained from an ad-hoc segmentation model based on a Gaussian Mixture Models 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, 46 progressive supranuclear palsy, and 60 corticobasal syndrome. In addition, 82 age-matched healthy participants were recruited as controls (HCs). ChP volume was significantly larger in patients with FTLD 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 CDR plus NACC FTLD, including patients at very early stage of the disease. Interestingly, ChP volume correlated with serum NfL, cognitive/behavioral deficits, and with patterns of cortical atrophy. Finally, ChP volume seemed to discriminate HC from patients with FTLD better than other previously identified brain structure volumes.

Discussion: Considering the clinical, pathologic, 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.

Publication types

Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Choroid Plexus / diagnostic imaging
Choroid Plexus / pathology
Frontotemporal Dementia* / diagnosis
Frontotemporal Lobar Degeneration* / pathology
Humans
Neurodegenerative Diseases*
Patient Acuity

Substances

Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding