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.
Neurology. 2023 Sep 19;101(12):e1218-e1230. doi: 10.1212/WNL.0000000000207600. Epub 2023 Jul 27.
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.
Participants included patients meeting clinical criteria for a probable syndrome in the FTLD spectrum. Structural brain MRI imaging, serum neurofilament light (NfL), serum phosphorylated-Tau (p-Tau), 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.
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.
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.
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.
脉络丛（ChP）正成为神经退行性疾病病理生理学中的关键脑结构。在这项观察性研究中，我们对额颞叶变性（FTLD）谱系的大量患者进行了脉络丛体积研究，以探讨脉络丛体积与其他疾病特异性生物标志物之间的可能联系。
参与者包括符合 FTLD 谱系中可能综合征临床标准的患者。收集结构脑 MRI 成像、血清神经丝轻链（NfL）、血清磷酸化 Tau（p-Tau）以及认知和行为数据。使用基于高斯混合模型算法的专门分割模型获得 MRI 脉络丛体积。
本研究共纳入 316 名 FTLD 谱系患者，具体为 135 名行为变异型额颞叶痴呆（bvFTD）患者、75 名原发性进行性失语症患者、46 名进行性核上性麻痹患者和 60 名皮质基底节综合征患者。此外，还招募了 82 名年龄匹配的健康参与者作为对照组（HCs）。与 HC 相比，FTLD 患者的脉络丛体积明显更大，跨越了临床亚型。此外，我们发现根据 CDR 加 NACC FTLD 对疾病严重程度进行分层的 HC 和患者之间的脉络丛体积存在显著差异，包括疾病非常早期的患者。有趣的是，脉络丛体积与血清 NfL、认知/行为缺陷以及皮质萎缩模式相关。最后，与其他先前确定的脑结构体积相比，脉络丛体积似乎可以更好地区分 HC 与 FTLD 患者。
考虑到疾病的临床、病理和遗传异质性，ChP 可能代表了 FTLD 谱中的一种潜在生物标志物，特别是在疾病的早期阶段。需要进一步的纵向研究来确定其在疾病发病和进展中的作用。
本研究提供了 III 级证据，表明 MRI 扫描测量的脉络丛体积可帮助区分 FTLD 患者与健康对照者，并可用于描述疾病严重程度。
